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Sample records for genes apob lpl

  1. Genetic association study of selected candidate genes (ApoB, LPL, Leptin and telomere length in obese and hypertensive individuals

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    Saini Divyalakshmi

    2009-09-01

    Full Text Available Abstract Background A genetic study was carried out among obese and hypertensive individuals from India to assess allelic association, if any, at three candidate loci: Apolipoprotein B (ApoB minisatellite and two tetranucleotide repeat loci; LPL (Lipoprotein lipase and Leptin. Attempt has also been made to find out whether telomere length attrition is associated with hypertension and obese individuals. Methods Venous blood samples were collected from 37 normal, 35 obese and 47 hypertensive individuals. Genomic DNA was extracted from peripheral blood mononuclear cells (PBMC and PCR amplifications were achieved using locus specific primers. Genotyping of ApoB minisatellite was performed using 4% polyacrylamide gel electrophoresis (PAGE followed by silver staining, whereas LPL and Leptin loci were genotyped using ALF Express™ DNA sequencer. Telomere length was determined using a recently developed real time based quantitative PCR, where the relative telomere length was determined by calculating the relative ratio of telomere (T and single copy gene (S PCR products which is expressed as T/S ratio. Results All the three loci are highly polymorphic, display high heterozygosity and conform to Hardy-Weinberg's equilibrium expectations. ApoB minisatellite displayed 14 alleles, whereas LPL and Leptin tetranucleotide loci were having 9 and 17 alleles, respectively. Interestingly two new alleles (9 and 11 repeats were detected at ApoB locus for the first time. The alleles at Leptin locus were classified as Class I (lower alleles: 149-200 bp and Class II alleles (higher alleles: >217 bp. Higher alleles at ApoB (>39 repeats, predominant allele 9 at LPL and alleles 164 bp and 224 bp at Leptin loci have shown allelic association with hypertensive individuals. After adjusting the influence of age and gender, the analysis of co-variance (ANCOVA revealed the relative telomere length (T/S ratio in hypertensive individuals to be (1.01 ± 0.021, which was

  2. Pathogenic classification of LPL gene variants reported to be associated with LPL deficiency

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    Rodrigues, Rute; Artieda, Marta; Tejedor, Diego

    2016-01-01

    BACKGROUND: Lipoprotein lipase (LPL) deficiency is a serious lipid disorder of severe hypertriglyceridemia (SHTG) with chylomicronemia. A large number of variants in the LPL gene have been reported but their influence on LPL activity and SHTG has not been completely analyzed. Gaining insight...

  3. Homozygosity for two point mutations in the lipoprotein lipase (LPL) gene in a patient with familial LPL deficiency: LPL(Asp9-->Asn, Tyr262-->His).

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    Rouis, M; Lohse, P; Dugi, K A; Lohse, P; Beg, O U; Ronan, R; Talley, G D; Brunzell, J D; Santamarina-Fojo, S

    1996-03-01

    Familial lipoprotein lipase (LPL) deficiency is an inherited disorder of lipoprotein metabolism characterized by hypertriglyceridemia and recurrent episodes of abdominal pain and pancreatitis. We have studied the genetic basis of LPL deficiency in a 62-year-old black male with undetectable pre- and post-heparin plasma LPL mass and activity, DNA sequence analysis of the patient's LPL cDNA and gene as well as digestion with Bcl I and Asu I revealed that the proband is a homozygote for two separate gene defects. One mutation changed a G to an A, resulting in the conversion of amino acid 9 of the mature protein, aspartic acid (GAC), to asparagine (AAC). The second substitution, a C for a T, replaced tyrosine (TAC) at residue 262 with histidine (CAC). Northern blot analysis of monocyte-derived macrophage RNA demonstrated the presence of LPL mRNA of approximately normal size and quantity when compared to control. Expression of both mutations separately (pCMV-9 and pCMV-262) or in combination (pCMV-9+262) in human embryonal kidney-293 cells demonstrated that LPL-9 had approximately 80% the specific activity of wild type LPL, but LPL-262 and LPL-9+262 had no enzymic activity, thus establishing the functional significance of the LPL-262 defect. Despite an absolute deficiency of LPL mass and activity demonstrated by analysis of patient post-heparin plasma, in vitro expression of both LPL mutants was normal, suggesting that the absence of LPL in patient post-heparin plasma was a result of altered in vivo processing. Analysis of the heparin binding properties of the mutant enzymes by heparin-Sepharose affinity chromatography indicated that most of the LPL-262 mass was present in an inactive peak, which like the normal LPL monomer, eluted at 0.8 M NaCl. Thus, the Tyr262 --> His mutation may alter the stability of the LPL dimer, leading to the formation of inactive LPL-262 monomer which exhibits reduced heparin affinity. Based on these results, we propose that, in vivo, enhanced

  4. Cloning and tissue expression characterization of the chicken APOB gene.

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    Zhang, Sen; Shi, Hui; Li, Hui

    2007-01-01

    Apolipoprotein B (APOB) serves an essential role in the assembly and secretion of triglyceride-rich lipoproteins and lipids transport. This study was designed to clone the full-length cDNA of the chicken APOB gene, to characterize the expression profile, and investigate the differential expression between layer and broiler of the chicken APOB gene. The full-length cDNA sequence (14,150-bp) that contained a 13,896-bp ORF encoding 4,631 amino acids was obtained by RT-PCR, RACE, and bioinformatics analysis. qReal-Time PCR analysis showed that the chicken APOB gene was highly expressed in kidney, liver, and intestine. The results of differential expression showed that the APOB gene was more highly expressed in intestine and kidney in Bai'er layer than in broiler, but there was no significant difference in liver between the two breeds. The results of this study provided basic molecular information for studying the role of APOB in the energy transportation in avian species.

  5. LPL gene expression is associated with poor prognosis in CLL and closely related to NOTCH1 mutations

    DEFF Research Database (Denmark)

    Kristensen, Louise; Kielsgaard Kristensen, Thomas; Abildgaard, Niels;

    2016-01-01

    these markers. AIM: To evaluate LPL gene expression together with the well-established prognostic markers of CLL and investigate correlations with more recently identified prognostic markers, NOTCH1 and TP53 mutations. METHODS: On 149 patients LPL gene expression was analyzed by real-time RT-PCR. Exon 34...... of NOTCH1 was PCR amplified and directly sequenced. RESULTS: LPL gene expression could be measured as a categorical variable (LPL+/LPL-) and was associated with time to treatment (p... and new prognostic markers, 3 out of 4 patients, who received treatment within 24 months after diagnosis, were LPL+ (p=0.03). There was a strong correlation between NOTCH1 mutation and LPL+ (p=0.005). The unfavorable prognosis of LPL+ was maintained in CLL with wild-type NOTCH1. CONCLUSIONS: NOTCH1...

  6. Spectrum of mutations of the LPL gene identified in Italy in patients with severe hypertriglyceridemia.

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    Rabacchi, Claudio; Pisciotta, Livia; Cefalù, Angelo B; Noto, Davide; Fresa, Raffaele; Tarugi, Patrizia; Averna, Maurizio; Bertolini, Stefano; Calandra, Sebastiano

    2015-07-01

    Monogenic hypertriglyceridemia (HTG) may result from mutations in some genes which impair the intravascular lipolysis of triglyceride (TG)-rich lipoproteins mediated by the enzyme Lipoprotein lipase (LPL). Mutations in the LPL gene are the most frequent cause of monogenic HTG (familial chylomicronemia) with recessive transmission. The LPL gene was resequenced in 149 patients with severe HTG (TG > 10 mmol/L) and 106 patients with moderate HTG (TG > 4.5 and <10 mmol/L) referred to tertiary Lipid Clinics in Italy. In the group of severe HTG, 26 patients (17.4%) were homozygotes, 9 patients (6%) were compound heterozygotes and 15 patients (10%) were simple heterozygotes for rare LPL gene variants. Single or multiple episodes of pancreatitis were recorded in 24 (48%) of these patients. There was no difference in plasma TG concentration between patients with or without a positive history of pancreatitis. Among moderate HTG patients, six patients (5.6%) were heterozygotes for rare LPL variants; two of them had suffered from pancreatitis. Overall 36 rare LPL variants were found, 15 of which not reported previously. Systematic analysis of close relatives of mutation carriers led to the identification of 44 simple heterozygotes (plasma TG 3.2 ± 4.1 mmol/L), none of whom had a positive history of pancreatitis. The prevalence of rare LPL variants in patients with severe or moderate HTG, referred to tertiary lipid clinics, was 50/149 (33.5%) and 6/106 (5.6%), respectively. Systematic analysis of relatives of mutation carriers is an efficient way to identify heterozygotes who may develop severe HTG. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  7. Familial lipoprotein lipase deficiency caused by known (G188E) and novel (W394X) LPL gene mutations.

    Science.gov (United States)

    Hooper, A J; Crawford, G M; Brisbane, J M; Robertson, K; Watts, G F; van Bockxmeer, F M; Burnett, J R

    2008-01-01

    Lipoprotein lipase (LPL) is the key enzyme in the catabolism of triglyceride-rich lipoproteins in the circulation. Familial LPL deficiency is characterized by hypertriglyceridaemia and absence of LPL activity. We report a case of LPL deficiency in a 43-year-old woman, who initially presented in childhood with chylomicronaemia syndrome. At that time, her plasma triglyceride concentration was approximately 30 mmol/L and post-heparin lipolytic activity was very low. In addition to having the known missense mutation LPL G188E, the patient was also found to have a novel nonsense mutation in exon 8, namely LPL W394X. The novel substitution in exon 8 (c.1262G > A) predicts a truncated protein product of 393 amino acids that lacks the carboxylterminal 12% of the mature LPL. Trp(394) is part of a cluster of exposed tryptophan residues in the carboxyl-terminal domain of LPL important for binding lipid substrate. Of 11 members from her three-generation family, three were heterozygotes for G188E (mean plasma triglyceride, 3.5 +/- 2.0 mmol/L), whereas six were heterozygotes for W394X (triglyceride, 4.3 +/- 1.8 mmol/L). In summary, we describe a case of familial LPL deficiency caused by compound heterozygosity for known (G188E) and novel (W394X) LPL gene mutations.

  8. Diagnostic value of post-heparin lipase testing in detecting common genetic variants in the LPL and LIPC genes

    NARCIS (Netherlands)

    M. van Hoek (Mandy); G.M. Dallinga-Thie (Geesje); E.W. Steyerberg (Ewout); E.J.G. Sijbrands (Eric)

    2009-01-01

    textabstractPost-heparin lipoprotein lipase and hepatic lipase activities are used to identify primary disorders of triglyceride and HDL-cholesterol metabolism. Their ability to identify common variants in the lipoprotein lipase (LPL) and hepatic lipase (LIPC) genes is unclear. To investigate the ab

  9. Mutational analysis of the LDL receptor and APOB genes in Mexican individuals with autosomal dominant hypercholesterolemia.

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    Vaca, Gerardo; Vàzquez, Alejandra; Magaña, Marìa Teresa; Ramìrez, Marìa Lourdes; Dàvalos, Ingrid P; Martìnez, Esperanza; Marìn, Bertha; Carrillo, Gabriela

    2011-10-01

    The goal of this project was to identify families with autosomal dominant hypercholesterolemia (ADH) to facilitate early detection and treatment and to provide genetic counselling as well as to approximate the mutational diversity of ADH in Mexico. Mutational analysis of the LDLR and APOB genes in 62 index cases with a clinical and/or biochemical diagnosis of ADH was performed. Twenty-five mutations (24 LDLR, 1 APOB) were identified in 38 index cases. A total of 162 individuals with ADH were identified using familial segregation analysis performed in 269 relatives of the index cases. In addition, a novel PCSK9 mutation, c.1850 C>A (p.Ala617Asp), was detected. The LDLR mutations showed the following characteristics: (1) four mutations are novel: c.695 -1G>T, c.1034_1035insA, c.1586 G>A, c.2264_2273del; (2) the most common mutations were c.682 G>A (FH-Mexico), c.1055 G>A (FH-Mexico 2), and c.1090 T>C (FH-Mexico 3); (3) five mutations were identified in 3 or more apparently unrelated probands; (4) three mutations were observed in a true homozygous state; and (5) four index cases were compound heterozygous, and one was a carrier of two mutations in the same allele. These results suggest that, in Mexico, ADH exhibits allelic heterogeneity with 5 relatively common LDLR mutations and that mutations in the APOB gene are not a common cause of ADH. This knowledge is important for the genotype-phenotype correlation and for optimising both cholesterol lowering therapies and mutational analysis protocols. In addition, these data contribute to the understanding of the molecular basis of ADH in Mexico.

  10. Polymorphisms in the LPL and CETP Genes and Haplotype in the ESR1 Gene Are Associated with Metabolic Syndrome in Women from Southwestern Mexico.

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    Cahua-Pablo, José Ángel; Cruz, Miguel; Méndez-Palacios, Abigail; Antúnez-Ortiz, Diana Lizzete; Vences-Velázquez, Amalia; del Carmen Alarcón-Romero, Luz; Parra, Esteban Juan; Tello-Flores, Vianet Argelia; Leyva-Vázquez, Marco Antonio; Valladares-Salgado, Adán; Pérez-Macedonio, Claudia Paola; Flores-Alfaro, Eugenia

    2015-09-08

    Metabolic syndrome (MetS) is a combination of metabolic disorders associated with an increased risk for cardiovascular disease (CVD). Studies in women reported associations between polymorphisms in ESR1, LPL and CETP genes and MetS. Our aim was to evaluate the association between variants in ESR1, LPL and CETP genes with MetS and its components. Four hundred and eighty women were analyzed, anthropometric features and biochemical profiles were evaluated, and genotyping was performed by real-time PCR. We found an association with elevated glucose levels (odds ratio (OR) = 2.9; p = 0.013) in carrying the AA genotype of rs1884051 in the ESR1 gene compared with the GG genotype, and the CC genotype of rs328 in the LPL gene was associated with MetS compared to the CG or GG genotype (OR = 2.8; p = 0.04). Moreover, the GA genotype of rs708272 in the CETP gene is associated with MetS compared to the GG or AA genotype (OR = 1.8; p = 0.006). In addition the ACTCCG haplotype in the ESR1 gene is associated with a decrease in the risk of MetS (OR = 0.02; p < 0.001). In conclusion, our results show the involvement of the variants of ESR1, LPL and CETP genes in metabolic events related to MetS or some of its features.

  11. Polymorphisms in the LPL and CETP Genes and Haplotype in the ESR1 Gene Are Associated with Metabolic Syndrome in Women from Southwestern Mexico

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    José Ángel Cahua-Pablo

    2015-09-01

    Full Text Available Metabolic syndrome (MetS is a combination of metabolic disorders associated with an increased risk for cardiovascular disease (CVD. Studies in women reported associations between polymorphisms in ESR1, LPL and CETP genes and MetS. Our aim was to evaluate the association between variants in ESR1, LPL and CETP genes with MetS and its components. Four hundred and eighty women were analyzed, anthropometric features and biochemical profiles were evaluated, and genotyping was performed by real-time PCR. We found an association with elevated glucose levels (odds ratio (OR = 2.9; p = 0.013 in carrying the AA genotype of rs1884051 in the ESR1 gene compared with the GG genotype, and the CC genotype of rs328 in the LPL gene was associated with MetS compared to the CG or GG genotype (OR = 2.8; p = 0.04. Moreover, the GA genotype of rs708272 in the CETP gene is associated with MetS compared to the GG or AA genotype (OR = 1.8; p = 0.006. In addition the ACTCCG haplotype in the ESR1 gene is associated with a decrease in the risk of MetS (OR = 0.02; p < 0.001. In conclusion, our results show the involvement of the variants of ESR1, LPL and CETP genes in metabolic events related to MetS or some of its features.

  12. Polymorphisms in the LPL and CETP Genes and Haplotype in the ESR1 Gene Are Associated with Metabolic Syndrome in Women from Southwestern Mexico

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    Cahua-Pablo, José Ángel; Cruz, Miguel; Méndez-Palacios, Abigail; Antúnez-Ortiz, Diana Lizzete; Vences-Velázquez, Amalia; del Carmen Alarcón-Romero, Luz; Parra, Esteban Juan; Tello-Flores, Vianet Argelia; Leyva-Vázquez, Marco Antonio; Valladares-Salgado, Adán; Pérez-Macedonio, Claudia Paola; Flores-Alfaro, Eugenia

    2015-01-01

    Metabolic syndrome (MetS) is a combination of metabolic disorders associated with an increased risk for cardiovascular disease (CVD). Studies in women reported associations between polymorphisms in ESR1, LPL and CETP genes and MetS. Our aim was to evaluate the association between variants in ESR1, LPL and CETP genes with MetS and its components. Four hundred and eighty women were analyzed, anthropometric features and biochemical profiles were evaluated, and genotyping was performed by real-time PCR. We found an association with elevated glucose levels (odds ratio (OR) = 2.9; p = 0.013) in carrying the AA genotype of rs1884051 in the ESR1 gene compared with the GG genotype, and the CC genotype of rs328 in the LPL gene was associated with MetS compared to the CG or GG genotype (OR = 2.8; p = 0.04). Moreover, the GA genotype of rs708272 in the CETP gene is associated with MetS compared to the GG or AA genotype (OR = 1.8; p = 0.006). In addition the ACTCCG haplotype in the ESR1 gene is associated with a decrease in the risk of MetS (OR = 0.02; p < 0.001). In conclusion, our results show the involvement of the variants of ESR1, LPL and CETP genes in metabolic events related to MetS or some of its features. PMID:26370976

  13. RFLPs of the APOB gene: comparative study between Greeks and southern Italian peoples.

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    De Benedictis, G; Leone, O; Falcone, E; Rose, G; Brancati, C; Carotenuto, L

    1993-06-01

    Restriction fragment length polymorphisms (RFLPs) at codons 2488 (XbaI), 3611 (MspI), and 4154 (EcoRI) of the apolipoprotein B gene were investigated in sample groups from Athens (Greece) and Calabria (southern Italy) to verify whether the distribution of the APOB gene variants in Calabria, where Greek colonization occurred in the eighth century B.C., reflects that of the present Greek population. A sample from Apulia, a southern Italian region having a history different from that of Calabria, was also analyzed. Three specific DNA regions, each containing the polymorphic site, were amplified by polymerase chain reaction on 243 samples, and the restriction data for the three groups were compared. The allelic frequencies of the samples from Apulia and Greece showed variability patterns that agree with those found in Caucasians, whereas the Calabrian sample shows remarkable peculiarities, mainly for the EcoRI RFLP. Linkage disequilibrium analyses of pairs of markers showed strong D linkage values between X-M markers, whereas the D linkage values between M-R markers were too small to be reliably estimated. Last, for both Apulians and Greeks, X-R markers showed linkage disequilibrium, whereas for Calabrians they did not. Estimates of XMR haplotypic frequencies were computed; they were found to be appreciably different between Calabrian and Greek samples, whereas the frequencies in the Apulian sample were approximately midway between those in Calabrians and Greeks.

  14. Correlation between the Xba I polymorphism of apoB gene and serum lipid profiles in Li ethnic group.

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    Liu, Yue-Li; Zhang, Yun-Bo; Li, Ying; Ma, Rui-Lian; Cai, Wang-Wei; Lin-Jiang, Li; Wang, Tian-Song; Yao, Zhen

    2014-01-01

    To study correlation between the Xba I polymorphism of apoB gene and plasma lipid profiles in Li ethnic group. Total 151 cases of healthy Li people were recruited randomly by cluster sampling and 200 Han people were recruited as control; blood was drawn to analyze Xba I polymorphism distribution of apoB gene and serum lipid levels. There were lower serum total cholesterol (TC) and low density lipoprotein cholesterol (LDL-C) levels in serum of Li people; while, high density lipoprotein cholesterol (HDL-C), X-/X+ genotype and X+ allele frequencies exhibited higher levels than Han people. Interestingly, HDL-C level was reduced, while LDL-C level was enhanced in subjects carrying heterozygous (X-/X+) genotype compared to homozygous (X-/X-) genotype. Additionally, there were no difference in serum level of triglyceride, TC, apoprotein A (apo A) and apoprotein B (apo B) between Li and Han people, the same results were showed between X-/X+ and X-/X- genotype carriers. Xba I polymorphism of apoB gene is correlated to the profiles of serum lipid level, X-/X+ genotype carriers are phenotyped with higher LDL-C level and lower level of HDL-C in Li ethnic group. Copyright © 2014 Hainan Medical College. Published by Elsevier B.V. All rights reserved.

  15. Correlation between the Xba Ipolymorphism of apoB gene and serumlipid profiles in Li ethnic group

    Institute of Scientific and Technical Information of China (English)

    Yue-Li Liu; Yun-Bo Zhang; Ying Li; Rui-Lian Ma; Wang-Wei Cai; Li Lin-Jiang; Tian-Song Wang; Zhen Yao

    2014-01-01

    Objective: To study correlation between the XbaⅠpolymorphism of apoB gene and plasma lipid profiles in Li ethnic group. Methods: Total 151 cases of healthy Li people were recruited randomly by cluster sampling and 200 Han people were recruited as control; blood was drawn to analyze XbaⅠpolymorphism distribution of apoB gene and serum lipid levels. Results: There were lower serum total cholesterol (TC) and low density lipoprotein cholesterol (LDL-C) levels in serum of Li people; while, high density lipoprotein cholesterol (HDL-C), X-/X+ genotype and X+ allele frequencies exhibited higher levels than Han people. Interestingly, HDL-C level was reduced, while LDL-C level was enhanced in subjects carrying heterozygous (X-/X+) genotype compared to homozygous (X-/X-) genotype. Additionally, there were no difference in serum level of triglyceride, TC, apoprotein A (apo A) and apoprotein B (apo B) between Li and Han people, the same results were showed between X-/X+ and X-/X- genotype carriers. Conclusions: XbaⅠpolymorphism of apoB gene is correlated to the profiles of serum lipid level, X-/X+ genotype carriers are phenotyped with higher LDL-C level and lower level of HDL-C in Li ethnic group.

  16. Polymorphisms in NOS3, MTHFR, APOB and TNF-α Genes and Risk of Coronary Atherosclerotic Lesions in Iranian Patients.

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    Heidari, Mohammad Mehdi; Khatami, Mehri; Hadadzadeh, Mehdi; Kazemi, Mahbobeh; Mahamed, Sahar; Malekzadeh, Pegah; Mirjalili, Massomeh

    2016-02-01

    Atherosclerosis is a complex multifocal arterial disease involving interactions between multiple genetic and environmental factors. In the present study, we investigated the possible association between NOS3 (rs1799983), MTHFR (rs1801133), APOB (rs5742904) and TNF-α (rs361525) polymorphisms and the risk of coronary atherosclerotic lesions in Iranian patients. In the case-control study, 108 patients with coronary atherosclerosis disease and 95 control subjects with no family history of cardiovascular disease were enrolled. Genotypes for NOS3, MTHFR, APOB and TNF-α polymorphisms were identified using polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP). We specifically detected the NOS3 TT genotype in 12 patients (11.11%) and did not find the same genotype in any of the controls. The frequencies of T allele in patients and the controls were 24% and 17.8%, respectively. The prevalence of the MTHFR TT genotype was 16.7% in patients and 2.2% in control groups. The prevalence of the APOB-100 (R3500Q) mutation in this patient population was 0%. The frequency of the A allele in the TNF-α gene was 11.1% and 11% in patients and controls, respectively, and the AA genotype was undetected. Our results show a significant association of NOS3 and MTHFR gene polymorphisms with coronary atherosclerotic lesions. Therefore, these variants might influence the risk of coronary artery disease, specifically in the Iranian population.

  17. Association of the HindIII and S447X Polymorphisms in LPL Gene with Hypertension and Type 2 Diabetes in Mexican Families

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    Salvador Muñoz-Barrios

    2012-01-01

    Full Text Available Lipoprotein lipase (LPL is a key enzyme in lipid metabolismand is associatedwith obesity, dyslipidemias, hypertension (HTN and type 2 diabetes mellitus (T2DM. LPL gene polymorphisms can be related with the development of cardiovascular risk factors. The present study was conducted to analyze the relationship of the HindIII and S447X polymorphisms in LPL gene with cardiovascular risk factors in Mexican families. The study population comprised ninety members of 30 Mexican families, in which an index case had obesity, were included in the study. We evaluated the body composition by bioelectrical impedance. Peripheral blood samples were collected to determine biochemical parameters. Screening for both polymorphisms was made by PCR-RFLPs. In the parents, both polymorphisms were in Hardy-Weinberg’s equilibrium. We found that the genotype T/T of HindIII was associated with diastolic blood pressure ≧ 85 mmHg (OR = 1.1; p = 0.011, whereas the genotype C/C of S447X was associated with systolic blood pressure ≧ 130 mmHg (OR = 1.2; p < 0.001, diastolic blood pressure ≧ 85 mmHg (OR = 1.3; p < 0.001, T2DM (OR = 1.3; p < 0.001 and with increase of total cholesterol (β = 23.6 mg/mL; p = 0.03. These data suggest that the HindIII and S447X LPL gene polymorphisms can confer susceptibility for the development of hypertension and T2DM in Mexican families.

  18. Genetic study of common variants at the Apo E, Apo AI, Apo CIII, Apo B, lipoprotein lipase (LPL and hepatic lipase (LIPC genes and coronary artery disease (CAD: variation in LIPC gene associates with clinical outcomes in patients with established CAD

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    Sorropago Giovanni

    2003-09-01

    Full Text Available Abstract Background Current evidence demonstrates that positive family history and several alterations in lipid metabolism are all important risk factors for coronary artery disease (CAD. All lipid abnormalities themselves have genetic determinants. Thus, objective of this study was to determine whether 6 genetic variants potentially related to altered lipid metabolism were associated with CAD and with lipid abnormalities in an Italian population. These genetic variables were: apolipoprotein E (Apo E, Apo AI, Apo CIII, Apo B, lipoprotein lipase (LPL and the hepatic lipase (LIPC genes. Furthermore, an 8 years prospective analysis of clinical cardiovascular events was related to the various genetic markers. Methods 102 subjects with established coronary artery disease and 104 unrelated normal subjects were studied. CAD Patients were followed up for 8 years, and clinical CAD outcomes (a second coronary angioplasty (PTCA, myocardial infarction, coronary artery by-pass graft (CABG, cardiovascular deaths, available from 60 subjects, were related to the genetic variants by multiple regression analysis. Results. Of the six lipid loci studied (for a total of 11 polymorphisms only the apolipoprotein E, Apo B and LIPC polymorphisms distinguished between case and controls. However, multivariate analysis accounting for clinical and metabolic predictors of CAD showed that only the ApoB Xba1 and ApoE4 polymorphism associated with CAD in this Italian population. When lipid parameters were related to genotypes, the ApoE, ApoB, and LIPC gene polymorphisms were associated to various markers of dyslipidaemia in the CAD patients, confirming previous reports. When the occurrence of a second cardiovascular event was related to genotypes, an independent role was observed for the LIPC gene T202T variant. Conclusions variation in LIPC (hepatic lipase gene associates with clinical outcomes in Italian patients with established CAD. Further studies on the LIPC gene in CAD

  19. 藏绵羊脂蛋白脂酶基因克隆及序列分析%Tibetan Sheep LPL Gene Clone and Bioinformatic Analysis

    Institute of Scientific and Technical Information of China (English)

    高思; 徐亚欧; 毛亮; 邵欢欢; 杨虎林; 舒浩国

    2011-01-01

    [目的]为深入研究藏绵羊肉用性能的遗传调控与营养代谢关系.[方法]利用RT-PCR和T-A克隆技术获得了藏绵羊LPL基因,并对其进行生物信息学分析.[结果]藏绵羊LPL编码基因全长1437 bp,编码478个氨基酸.将藏绵羊LPL基因及氨基酸序列分别与GenBank中公布的11种动物进行序列一致率比对,发现藏绵羊与所选动物的LPL基因序列一致率在84.6%-99.6%,LPL氨基酸序列一致率在88.8%-99.0%.藏绵羊与普通绵羊LPL基因存在6个位点核苷酸差异,其中有一个核苷酸位点的差异没有引起相应氨基酸的改变,其余5个住点核苷酸的不同都引起了氨基酸的差异.[结论]该研究可为了解LPL基因的演化关系及作用机理提供资料.%[ Objective ] The aim was to deeply study the relationship between the genetic regulation of meat performance of Tibetan sheep and nutrition and metabolism. [ Method ] The LPL coding gene of Tibetan sheep was cloned by reverse-translation PCR and T-A clone technology,then it was analyzed by Bioinformatics software. [ Result] The results showed that LPL gene of Tibetan sheep contained 1437 bp nucleotides and encoded 478 amino acids. The multiple sequence alignment such as Tibetan sheep, sheep, goat, cattle, yak, pig, dog, cat, baboon, orangutan, human, Norway rat and rattus showed that the total homologous rate of LPL gene was 84.6% - 99.6%, and the homologous rate of amino acids was 88.8% ~ 99.0%. Moreover,6 different nucleotides were foumd between Tibetan sheep and common sheep. One of these nucleotide was synonymous codon so that the amino acid which the synonymous codon encoded was identical between Tibetan sheep and common sheep,and the other five nucleotides which encoded different amino acids between Tibetan sheep and common sheep. [ Conclusion ] The study can provide reference for knowing the evolution relation of LPL gene and its mechanism of action.

  20. ApoB-100, ApoE and CYP7A1 gene polymorphisms in Mexican patients with cholesterol gallstone disease

    Institute of Scientific and Technical Information of China (English)

    Sánchez-Cuén; Jaime; Aguilar-Medina; Maribel; Arámbula-Meraz; Eliakym; Romero-Navarro; José; Granados; Julio; Sicairos-Medina; Laura; Ramos-Payán; Rosalío

    2010-01-01

    AIM: To determine the possible association of the ApoB100 (Xba Ⅰ ), ApoE (Hha Ⅰ ) and CYP7A1 (Bsa Ⅰ ) gene polymorphisms, with the development of cholesterol gallstone disease (GD) in a Mexican population. METHODS: The polymorphisms were analyzed by polymerase chain reaction followed by restriction fragment length polymorphism, in two groups matched by ethnicity, age and sex: patients with GD (n = 101) and stone-free control subjects (n = 101). RESULTS: Allelic frequencies in patients and controls were: 34....

  1. A new but frequent mutation of apoB-100-apoB His3543Tyr.

    Science.gov (United States)

    Soufi, Muhidien; Sattler, Alexander M; Maerz, Winfried; Starke, Alexander; Herzum, Matthias; Maisch, Bernhard; Schaefer, Juergen R

    2004-05-01

    ApolipoproteinB 100 (apoB-100) is an important component of atherogenic lipoproteins such as LDL and serves as a ligand for the LDL-receptor. Familial defective apolipoproteinB 100 (FDB) is caused by a R3500Q mutation of the apoB gene and results in decreased binding of LDL to the LDL-receptor. So far FDB is the most frequent and best studied alteration of apoB-100. Apart from this, three other apoB mutations, R3500W, R3531C and R3480W, affecting binding to the LDL-receptor are known to date. We screened the apoB gene segment of codons 3448-3561 by denaturing gradient gel electrophoresis (DGGE) analysis in a total of 853 consecutively sampled German patients undergoing diagnostic coronary angiography for suspected CAD. By this, a new single base mutation was detected and confirmed by DNA sequencing. The mutation, CAC(3543)TAC results in a His3543Tyr substitution in apoB-100 (H3543Y). The prevalence of heterozygotes for H3543Y in the study population was 0.47% compared to 0.12% for the known Arg 3500 Gln (R3500Q) mutation. In conclusion, the new mutation is four times more frequent than "classical" FDB and thus appears to be the most common apoB mutation in Germany.

  2. Antisense oligonucleotide-induced alternative splicing of the APOB mRNA generates a novel isoform of APOB

    Directory of Open Access Journals (Sweden)

    Chew Shern L

    2007-01-01

    Full Text Available Abstract Background Apolipoprotein B (APOB is an integral part of the LDL, VLDL, IDL, Lp(a and chylomicron lipoprotein particles. The APOB pre-mRNA consists of 29 constitutively-spliced exons. APOB exists as two natural isoforms: the full-length APOB100 isoform, assembled into LDL, VLDL, IDL and Lp(a and secreted by the liver in humans; and the C-terminally truncated APOB48, assembled into chylomicrons and secreted by the intestine in humans. Down-regulation of APOB100 is a potential therapy to lower circulating LDL and cholesterol levels. Results We investigated the ability of 2'O-methyl RNA antisense oligonucleotides (ASOs to induce the skipping of exon 27 in endogenous APOB mRNA in HepG2 cells. These ASOs are directed towards the 5' and 3' splice-sites of exon 27, the branch-point sequence (BPS of intron 26–27 and several predicted exonic splicing enhancers within exon 27. ASOs targeting either the 5' or 3' splice-site, in combination with the BPS, are the most effective. The splicing of other alternatively spliced genes are not influenced by these ASOs, suggesting that the effects seen are not due to non-specific changes in alternative splicing. The skip 27 mRNA is translated into a truncated isoform, APOB87SKIP27. Conclusion The induction of APOB87SKIP27 expression in vivo should lead to decreased LDL and cholesterol levels, by analogy to patients with hypobetalipoproteinemia. As intestinal APOB mRNA editing and APOB48 expression rely on sequences within exon 26, exon 27 skipping should not affect APOB48 expression unlike other methods of down-regulating APOB100 expression which also down-regulate APOB48.

  3. Dietary ω-3 polyunsaturated fatty acid intake modulates impact of Insertion/Deletion polymorphism of ApoB gene on obesity risk in type 2 diabetic patients.

    Science.gov (United States)

    Rafiee, Masoumeh; Sotoudeh, Gity; Djalali, Mahmoud; Alvandi, Ehsan; Eshraghian, Mohammadreza; Sojoudi, Fereshteh; Koohdani, Fariba

    2016-10-01

    The goal of the study described here was to determine whether dietary ω-3 polyunsaturated fatty acid (PUFA) intake modulates the association between ApoB Ins/Del polymorphism and obesity in type 2 diabetic patients. In this cross-sectional study, 700 patients with type 2 diabetes were recruited in Tehran. Weight and waist circumference (WC) were measured, and body mass index (BMI) was calculated. Dietary intake was assessed using a validated semiquantitative food frequency questionnaire. ApoB genotyping was performed with 8% polyacrylamide gel electrophoresis. We observed a significant interaction between Ins/Del genotype and dietary ω-3 PUFA intake with respect to BMI, WC, and obesity risk in both unadjusted (P = 0.007, P = 0.001, and P = 0.021, respectively) and adjusted (P = 0.007, P = 0.04, and P = 0.002, respectively) samples. Thus, the carriers of the Del allele were only associated with lower BMI (P = 0.01) and WC (P = 0.002) among individuals with high ω-3 PUFA intake (≥0.6% of energy), but not in those with low ω-3 PUFA intake (obesity risk in carriers of the Del allele was about 1.6 times higher than that of Ins/Ins homozygotes (odds ratio = 1.59, 95% confidence interval: 1.05-2.52, P = 0.039). But with high ω-3 PUFA intake (≥0.6%), the risk was 0.46 times lower (odds ratio = 0.46, 95% confidence interval: 0.25-0.79, P = 0.003). Moreover, a similar interaction was observed in central obesity only in men after adjustment for confounder variables (P = 0.041). These findings support the hypothesis that a diet high in ω-3 PUFA (≥0.6%) can decrease the obesity risk in carriers of the Del allele of ApoB gene. Copyright © 2016 Elsevier Inc. All rights reserved.

  4. Calculation of LDL apoB

    NARCIS (Netherlands)

    Sniderman, A.D.; Tremblay, A.J.; Graaf, J. de; Couture, P.

    2014-01-01

    OBJECTIVES: This study tests the validity of the Hattori formula to calculate LDL apoB based on plasma lipids and total apoB. METHODS: In 2178 patients in a tertiary care lipid clinic, LDL apoB calculated as suggested by Hattori et al. was compared to directly measured LDL apoB isolated by ultracent

  5. Coalition of DNA polymorphisms of ApoB and ApoAI genes is related with coronary artery disease in Kazaks

    Institute of Scientific and Technical Information of China (English)

    Gang Huang; Hua Zhong; He-Man Re; Hong-Wei Mao; Qiang Niu; Ye-Hong Chi

    2012-01-01

    Objective To explore the relationship between polymorphisms of XbaI and MspI loci of apolipoprotein B (ApoB) gene and -75 bp,+83 bp loci of apolipoprotein AI (ApoAI) gene and coronary heart disease (CHD) in Kazaks of Xinjiang Uyghur Autonomous Region,China.Methods These loci were analyzed by PCR-restriction fragment length polymorphism (PCR-PFLP).Two hundred and five patients with CHD and two hundred and thirty six controls were involved.Results There were significant distinctions among low-density lipoprotein cholesterol (LDL-C),triglyceride (TG) and the ApoAI/ApoB ratio between the two groups,but no significant distinction among the polymorphism frequencies of the four sites between the two groups.The polymorphism coalition frequency of X-/Ms++/M1+-/M2++ (named Coalition 11) was significantly higher in CHD compared to the control group (14.6% vs.7.2%,P < 0.05).The level of total cholesterol (TC) in Coalition 1 1 was significantly higher and the level of the ApoAI/ApoB ratio in Coalition 11 was significantly lower than Coalition 1~10 in CHD patients.The level of the ApoAI/ApoB ratio of Coalition 11 was significantly lower than the Coalition 1~10 in control group.The levels of ApoAI/ApoB ratio of Coalition 3 were significantly higher compared to Coalition 11 in the two groups,respectively.The level of LDL-C of Coalition 3 was significantly lower than in the Coalition 11 in control group.The level of TC of Coalition 5 was significantly higher than Coalition 3 in the CHD group.The level of the ApoAI/ApoB ratio of Coalition 5 was significantly lower than in Coalition 3 or Coalition 1~10 of the two groups,respectively.The level of LDL-C of Coalition 5 was significantly higher than in Coalition 3 in control group.The ratio of ApoAI/ApoB was negatively related to TC,LDL-C and was positively related to HDL-C,both in CHD and control groups.Conclusion Coalition 11 of the 4 loci polymorphisms of the ApoB and ApoAI genes was correlated with CHD in Kazaks

  6. LPL gene mutation as the cause of severe hypertriglyceridemia in the course of ketoacidosis in a patient with newly diagnosed type 1 diabetes mellitus.

    Science.gov (United States)

    Nocoń-Bohusz, Julita; Wikiera, Beata; Basiak, Aleksander; Śmigiel, Robert; Noczyńska, Anna

    2016-02-18

    Wstęp. Ciężka hipertrójglicerydemia to stan, w którym stężenie trójglicerydów (TG) przekracza 1000 mg/dl. Za zaburzenie to mogą odpowiadać mutacje w genie lipazy lipoproteinowej (LPL), apolipoproteiny C2 (APOC2) i apolipoproteiny A5 (APOA5) dziedziczone w sposób autosomalnie recesywny. Cel. W pracy przedstawiamy pacjenta, u którego manifestacji klinicznej cukrzycy towarzyszyła kwasica metaboliczna oraz skrajna hiperlipidemia. Opis pacjenta. 2,5 letni chłopiec przyjęty został do szpitala z kwasicą ketonową (pH – 7,0, BE -20 mmol/l , HCO3 10 mmol/l), stężeniem glukozy 850 mg%, hiponatremią (Na 100 mmol/l) oraz hiperlipidemią (trójglicerydy (TG) 13493 mg/dl, cholesterol całkowity (TC) 734 mg/dl). Zastosowano leczenie, uzyskując prawidłowe glikemie oraz normalizację zaburzeń lipidowych. U dziecka rozpoznano heterozygotyczną mutację genu LPL. Intensywna insulinoterapia i prawidłowe wyrównanie metaboliczne cukrzycy typu 1 gwarantują prawidłowy lipidogram u pacjenta do chwili obecnej. Wniosek. Rozpoznając skrajną hipertrójglicerydemię w kwasicy ketonowej w przebiegu cukrzycy typu 1, należy ostrożnie interpretować wyniki badań laboratoryjnych oraz dążyć do wykonania badania genetycznego u pacjenta, także u najbliższych jego krewnych.

  7. Molecular cloning and expression analysis on LPL of Coilia nasus.

    Science.gov (United States)

    Wang, Meiyao; Xu, Dongpo; Liu, Kai; Yang, Jian; Xu, Pao

    2016-06-01

    Coilia nasus is one important commercial anadromous species which mainly distributed in the Yangtze River in China. At present, it has been on the "National Key Protective Species List" because of its severe resource damage. Lipid metabolism is very important during its long-distance migration. To make further research on lipid metabolism of C. nasus, we cloned lipoprotein lipase gene with homologous cloning method. A full-length cDNA of LPL of C. nasus was cloned from liver which covered 3537 bp with a 1519 bp open reading frame encoding 505 deduced amino acids whose molecular mass was 57.5 kDa and theoretical isoelectric point was 7.58. The deduced amino acids had high similarity with the reported LPL sequence of other species. It had typical conserved domain of LPL protein containing catalytic triad, N-linked glycosylation sites and conserved heparin-binding site, etc. We adopted quantitative real-time RT-PCR method to detect the mRNA expression of LPL of C. nasus in ten tissues including mesenteric adipose, liver, muscle, stomach, spleen, heart, head kidney, trunk kidney, gill and brain with β-actin as internal reference. LPL expressed in all the detected tissues. The highest expression was in mesenteric adipose, and followed by liver, muscle, stomach. Lipid expressed lowly in spleen, heart, head kidney, trunk kidney, gill and brain. The research on the cloning and differential expression of LPL of C. nasus will lay foundation for further research on lipid metabolism of C. nasus.

  8. Association of LPL-Hind III polymorphism with coronary artery disease in Macedonian population

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    Georgiev Antonio

    2013-03-01

    Full Text Available Objective: Coronary artery disease (CAD is a leading cause of high mortality and morbidity in worldwide. The Hind III polymorphism of the LPL gene (LPL-Hind III is a common variant and has been associated with plasma lipid and lipoprotein variability in population studies. Aim: Evaluation of the LPL-Hind III polymorphism as an independent risk factor for coronary artery disease in Macedonian population. Material and Methods: A polymerase chain reaction amplification and consecutive restriction enzyme digestion was used to reveal lipoprotein lipase, the intron 8 LPL-Hind III polymorphism. Study group included 114 randomized subjects with angiographically documented coronary artery stenosis (CAD group: 87 males, 27 females. Control group consisted of 35 patients (21 males and 14 females without significant stenosis in coronary arteries. Results: Independent multiple regression analysis of LDL plasma level and their correlation with LPL-Hind III polymorphism and analyzed risk factors: hypertension, diabetes, family history of CAD, physical activity, antilipidemic drugs and alcohol consumption, LDL, show statistically significant correlation with BMI, and also between LPL-Hind III and LDL plasma level. In the examined group, only triglycerides reached a statistically significant association with the LPL-Hind III polymorphism. Conclusion: In our study, the LPL-Hind III polymorphism was not identified as independent risk factor for CAD, but showed association with high triglycerides and LDL levels.

  9. Staphylococcus aureus Lpl Lipoproteins Delay G2/M Phase Transition in HeLa Cells.

    Science.gov (United States)

    Nguyen, Minh-Thu; Deplanche, Martine; Nega, Mulugeta; Le Loir, Yves; Peisl, Loulou; Götz, Friedrich; Berkova, Nadia

    2016-01-01

    The cell cycle is an ordered set of events, leading to cell growth and division into two daughter cells. The eukaryotic cell cycle consists of interphase (G1, S, and G2 phases), followed by the mitotic phase and G0 phase. Many bacterial pathogens secrete cyclomodulins that interfere with the host cell cycle. In Staphylococcus aureus four cyclomodulins have been described so far that all represent toxins and are secreted into the culture supernatant. Here we show that the membrane-anchored lipoprotein-like proteins (Lpl), encoded on a genomic island called νSaα, interact with the cell cycle of HeLa cells. By comparing wild type and lpl deletion mutant it turned out that the lpl cluster is causative for the G2/M phase transition delay and also contributes to increased invasion frequency. The lipoprotein Lpl1, a representative of the lpl cluster, also caused G2/M phase transition delay. Interestingly, the lipid modification, which is essential for TLR2 signaling and activation of the immune system, is not necessary for cyclomodulin activity. Unlike the other staphylococcal cyclomodulins Lpl1 shows no cytotoxicity even at high concentrations. As all Lpl proteins are highly conserved there might be a common function that is accentuated by their multiplicity in a tandem gene cluster. The cell surface localized Lpls' suggests a correlation between G2/M phase transition delay and host cell invasion.

  10. Staphylococcus aureus Lpl Lipoproteins Delay G2/M Phase Transition in HeLa Cells

    Science.gov (United States)

    Nguyen, Minh-Thu; Deplanche, Martine; Nega, Mulugeta; Le Loir, Yves; Peisl, Loulou; Götz, Friedrich; Berkova, Nadia

    2016-01-01

    The cell cycle is an ordered set of events, leading to cell growth and division into two daughter cells. The eukaryotic cell cycle consists of interphase (G1, S, and G2 phases), followed by the mitotic phase and G0 phase. Many bacterial pathogens secrete cyclomodulins that interfere with the host cell cycle. In Staphylococcus aureus four cyclomodulins have been described so far that all represent toxins and are secreted into the culture supernatant. Here we show that the membrane-anchored lipoprotein-like proteins (Lpl), encoded on a genomic island called νSaα, interact with the cell cycle of HeLa cells. By comparing wild type and lpl deletion mutant it turned out that the lpl cluster is causative for the G2/M phase transition delay and also contributes to increased invasion frequency. The lipoprotein Lpl1, a representative of the lpl cluster, also caused G2/M phase transition delay. Interestingly, the lipid modification, which is essential for TLR2 signaling and activation of the immune system, is not necessary for cyclomodulin activity. Unlike the other staphylococcal cyclomodulins Lpl1 shows no cytotoxicity even at high concentrations. As all Lpl proteins are highly conserved there might be a common function that is accentuated by their multiplicity in a tandem gene cluster. The cell surface localized Lpls' suggests a correlation between G2/M phase transition delay and host cell invasion. PMID:28083519

  11. Risk of chronic kidney disease in type 2 diabetes determined by polymorphisms in NOS3, APOB, KCNJ11, TCF7L2 genes as compound effect of risk genotypes combination

    Directory of Open Access Journals (Sweden)

    Anna Viktorovna Zheleznyakova

    2014-08-01

    Full Text Available Genetic susceptibility plays an important role in the risk of developing chronic complications in patients with type 2 diabetes mellitus (T2DM.AimsIn this study, we evaluated the possible association of the polymorphic variants that encode key renal damage mediators (endothelial dysfunction, lipid metabolism and insulin secretion/sensitivity with the risk of chronic kidney disease (CKD in patients with T2DM.Materials and MethodsWe enrolled 435 patients with T2DM using case-control study design. In 253 patients, we used non-overlapping criteria to form groups with/without CKD (defined as GFR<60 ml/min/1.73 m2 according to the duration of T2DM (≤5 years/≥10 years (n=75 and 178, respectively and analysed the following 4 polymorphic markers: I/D in ACE, ecNOS4a/4b in NOS3, I/D in APOB and e2/e3/e4 in APOE genes. We then divided 182 patients in groups with/without CKD (n=38 and 144, respectively regardless of the duration of diabetes and studied pro12ala in PPARG2, rs5219 in KCNJ11, rs12255372 in TCF7L2 and rs13266634 in SLC30A8 genes. Statistical analysis was performed using the χ2 test, and data were expressed as odds ratios (ORs with 95% confidence intervals (CIs. Values of p <0.05 indicated statistical significance.ResultsFour genes were found to have a significant association with CKD occurrence. For the eNOS3 the allele 4a and 4a/4a genotype was associated with a twofold CKD risk (OR=2.2/9.88 and the allele 4b and 4b/4b polymorphism were protective regarding CKD development (OR=0.44/0.45. For APOB I/D, the genotype DD was associated with lower risk of CKD [OR for DD=0.2 (95% CI: 0.05–0.88]. In the second group, genotype TT of TCF7L2 predisposed to CKD (OR=3.03, 95% CI: 1.07–8.58. For KCNJ11 group genotype AA predisposed to CKD (OR=2.25, 95% CI: 1.02–4.97 compared to the allele G (OR=0,57, 95% CI: 0.34–0.96.ConclusionsIn conclusion, our findings indicate a significant role of functional genetic variants associated with genes of

  12. A lipoprotein lipase (LPL)-specific monoclonal antibody, 88B8, that abolishes the binding of LPL to GPIHBP1

    DEFF Research Database (Denmark)

    Allan, Christopher M; Larsson, Mikael; Hu, Xuchen

    2016-01-01

    Lipoprotein lipase (LPL) contains two principal domains: an amino-terminal catalytic domain (residues 1-297) and a carboxyl-terminal domain (residues 298-448) that is important for binding lipids and binding GPIHBP1 (an endothelial cell protein that shuttles LPL to the capillary lumen). The LPL s...

  13. Apolipoprotein B-100 containing lipoprotein metabolism in subjects with lipoprotein lipase gene mutations (106/120)

    Science.gov (United States)

    Ooi, Esther M M; Russell, Betsy S; Olson, Eric; Sun, Sam Z; Diffenderfer, Margaret R; Lichtenstein, Alice H; Keilson, Leonard; Barrett, P Hugh R; Schaefer, Ernst J; Sprecher, Dennis L

    2012-01-01

    Objective We investigated the impact of lipoprotein lipase (LPL) gene mutations on apolipoprotein (apo) B-100 metabolism. Methods and Results We studied 3 subjects with familial LPL deficiency (FLD), 14 subjects heterozygous for the LPL gene mutations, Gly188Glu, Trp64Stop and Ile194Thr, and 10 control subjects. Very-low density lipoprotein (VLDL), intermediate-density lipoprotein (IDL) and low-density lipoprotein (LDL)-apoB-100 kinetics were determined in the fed state using stable isotope methods and compartmental modeling. Compared with controls, FLD had markedly elevated plasma triglycerides and lower VLDL-apoB-100 fractional catabolic rate (FCR), IDL-apoB-100 FCR, VLDL-to-IDL conversion and VLDL-apoB-100 production rate (PR) (ptriglyceride, VLDL- and IDL-apoB-100 concentrations, and lower VLDL- and IDL-apoB-100 FCR (ptriglycerides were not different but IDL-apoB-100 concentration and PR, and VLDL-to-IDL conversion were lower in Trp64Stop compared with controls (ptriglycerides. The changes in plasma triglycerides and apoB-100 kinetics are attributable to the effects of the LPL genotype. PMID:22095987

  14. The νSaα Specific Lipoprotein Like Cluster (lpl) of S. aureus USA300 Contributes to Immune Stimulation and Invasion in Human Cells.

    Science.gov (United States)

    Nguyen, Minh Thu; Kraft, Beatrice; Yu, Wenqi; Demircioglu, Dogan Doruk; Demicrioglu, Dogan Doruk; Hertlein, Tobias; Burian, Marc; Schmaler, Mathias; Boller, Klaus; Bekeredjian-Ding, Isabelle; Ohlsen, Knut; Schittek, Birgit; Götz, Friedrich

    2015-06-01

    All Staphylococcus aureus genomes contain a genomic island, which is termed νSaα and characterized by two clusters of tandem repeat sequences, i.e. the exotoxin (set) and 'lipoprotein-like' genes (lpl). Based on their structural similarities the νSaα islands have been classified as type I to IV. The genomes of highly pathogenic and particularly epidemic S. aureus strains (USA300, N315, Mu50, NCTC8325, Newman, COL, JH1 or JH9) belonging to the clonal complexes CC5 and CC8 bear a type I νSaα island. Since the contribution of the lpl gene cluster encoded in the νSaα island to virulence is unclear to date, we deleted the entire lpl gene cluster in S. aureus USA300. The results showed that the mutant was deficient in the stimulation of pro-inflammatory cytokines in human monocytes, macrophages and keratinocytes. Purified lipoprotein Lpl1 was further shown to elicit a TLR2-dependent response. Furthermore, heterologous expression of the USA300 lpl cluster in other S. aureus strains enhanced their immune stimulatory activity. Most importantly, the lpl cluster contributed to invasion of S. aureus into human keratinocytes and mouse skin and the non-invasive S. carnosus expressing the lpl gene cluster became invasive. Additionally, in a murine kidney abscess model the bacterial burden in the kidneys was higher in wild type than in mutant mice. In this infection model the lpl cluster, thus, contributes to virulence. The present report is one of the first studies addressing the role of the νSaα encoded lpl gene cluster in staphylococcal virulence. The finding that the lpl gene cluster contributes to internalization into non-professional antigen presenting cells such as keratinocytes highlights the lpl as a new cell surface component that triggers host cell invasion by S. aureus. Increased invasion in murine skin and an increased bacterial burden in a murine kidney abscess model suggest that the lpl gene cluster serves as an important virulence factor.

  15. Human apoB contributes to increased serum total apo(a level in LPA transgenic mice

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    Teivainen Päivi A

    2004-05-01

    Full Text Available Abstract Background The Lp(a lipoprotein (Lp(a consists of the polymorphic glycoprotein apolipoprotein(a (apo(a, which is attached by a disulfide bond to apolipoprotein B (apoB. Apo(a, which has high homology with plasminogen, is present only in primates and hedgehogs. However, transgenic mice and rabbits with high serum apo(a levels exist. Liver is the main site for apo(a synthesis, but the site of removal is uncertain. To examine differences between transgenic mice expressing the LPA gene and mice capable of forming Lp(a particles, LPA-YAC transgenic mice and hAPOB transgenic mice were crossed and their offspring examined. Results Comparison of LPA-YAC with LPA-YAC/hAPOB transgenic mice showed that LPA-YAC/hAPOB transgenic mice have higher serum total apo(a and total cholesterol level than mice lacking the hAPOB gene. However, hepatic apo(a mRNA level was higher in LPA-YAC transgenic mice than in LPA-YAC/hAPOB transgenic mice. Feeding of a high-cholesterol/high-fat diet to male LPA-YAC transgenic mice with or without the hAPOB gene resulted in reduced serum total apo(a and hepatic apo(a mRNA level. Conclusion In conclusion, the higher serum total apo(a level in LPA-YAC/hAPOB transgenic mice than in LPA-YAC transgenic mice is not caused by increased apo(a synthesis. Lower hepatic apo(a mRNA level in LPA-YAC/hAPOB than in LPA-YAC transgenic mice may suggest that the increase in total apo(a level is a result of apo(a accumulation in serum. Furthermore, observed higher serum total cholesterol level in LPA-YAC/hAPOB transgenic mice than either in wild type or LPA-YAC transgenic mice may further suggest that human APOB transgenicity is a factor that contributes to increased serum total apo(a and cholesterol levels. Our results on reduced serum total apo(a and hepatic apo(a mRNA levels in HCHF fed male LPA-YAC transgenic mice confirm earlier findings in females, and show that there are no sex difference in mechanisms for lowering apo(a level in

  16. Polymorphism in APOB associated with increased low-density lipoprotein levels in both genders in the general population

    DEFF Research Database (Denmark)

    Benn, Marianne; Nordestgaard, Børge G; Jensen, Jan S

    2005-01-01

    Rare mutations in APOB cause hypercholesterolemia. Whether common polymorphisms in APOB have similar effects remains controversial.......Rare mutations in APOB cause hypercholesterolemia. Whether common polymorphisms in APOB have similar effects remains controversial....

  17. Lipoprotein Metabolism in APOB L343V Familial Hypobetalipoproteinemia.

    Science.gov (United States)

    Hooper, Amanda J; Heeks, Liesl; Robertson, Ken; Champain, Danie; Hua, Jianmin; Song, Swithin; Parhofer, Klaus G; Barrett, P Hugh R; van Bockxmeer, Frank M; Burnett, John R

    2015-11-01

    Familial hypobetalipoproteinemia (FHBL) is a codominant disorder of lipoprotein metabolism characterized by decreased plasma concentrations of low-density lipoprotein (LDL)-cholesterol and apolipoprotein B (apoB). The objective was to examine the effect of heterozygous APOB L343V FHBL on postprandial triglyceride-rich lipoprotein (TRL) and fasting lipoprotein metabolism. Plasma incremental area under the curve apoB-48 and apoB-48 kinetics were determined after ingestion of a standardized oral fat load using compartmental modeling. Very low-density lipoprotein (VLDL)-, intermediate-density lipoprotein (IDL)-, and LDL-apoB kinetics were determined in the fasting state using stable isotope methods and compartmental modeling. The postprandial incremental area under the curve (0-10 h) in FHBL subjects (n = 3) was lower for large TRL-triglyceride (-77%; P < .0001), small TRL-cholesterol (-83%; P < .001), small TRL-triglyceride (-88%; P < .001), and for plasma triglyceride (-70%; P < .01) and apoB (-63%; P < .0001) compared with controls. Compartmental analysis showed that apoB-48 production was lower (-91%; P < .05) compared with controls. VLDL-apoB concentrations in FHBL subjects (n = 2) were lower by more than 75% compared with healthy, normolipidemic control subjects (P < .01). The VLDL-apoB fractional catabolic rate (FCR) was more than 5-fold higher in the FHBL subjects (P = .07). ApoB production rates and IDL- and LDL-apoB FCRs were not different between FHBL subjects and controls. We conclude that when compared to controls, APOB L343V FHBL heterozygotes show lower TRL production with normal postprandial TRL particle clearance. In contrast, VLDL-apoB production was normal, whereas the FCR was higher in heterozygotes compared with lean control subjects. These mechanisms account for the marked hypolipidemic state observed in these FHBL subjects.

  18. Rare and common variants in LPL and APOA5 in Thai subjects with severe hypertriglyceridemia: A resequencing approach.

    Science.gov (United States)

    Khovidhunkit, Weerapan; Charoen, Supannika; Kiateprungvej, Arunrat; Chartyingcharoen, Palm; Muanpetch, Suwanna; Plengpanich, Wanee

    2016-01-01

    Severe hypertriglyceridemia usually results from a combination of genetic and environmental factors. Few data exist on the genetics of severe hypertriglyceridemia in Asian populations. To examine the genetic variants of 3 candidate genes known to influence triglyceride metabolism, LPL, APOC2, and APOA5, which encode lipoprotein lipase, apolipoprotein C-II, and apolipoprotein A-V, respectively, in a large group of Thai subjects with severe hypertriglyceridemia. We identified sequence variants of LPL, APOC2, and APOA5 by sequencing exons and exon-intron junctions in 101 subjects with triglyceride levels ≥ 10 mmol/L (886 mg/dL) and compared with those of 111 normotriglyceridemic subjects. Six different rare variants in LPL were found in 13 patients, 2 of which were novel (1 heterozygous missense variant: p.Arg270Gly and 1 frameshift variant: p.Asp308Glyfs*3). Four previously identified heterozygous missense variants in LPL were p.Ala98Thr, p.Leu279Val, p.Leu279Arg, and p.Arg432Thr. Collectively, these rare variants were found only in the hypertriglyceridemic group but not in the control group (13% vs 0%, P hypertriglyceridemia. A common p.Gly185Cys APOA5 variant, in particular, was quite prevalent and potentially contributed to hypertriglyceridemia in this group of patients. Copyright © 2015 National Lipid Association. Published by Elsevier Inc. All rights reserved.

  19. Association of Polymorphisms of Genes Involved in Lipid Metabolism with Blood Pressure and Lipid Values in Mexican Hypertensive Individuals

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    Blanca Estela Ríos-González

    2014-01-01

    Full Text Available Hypertension and dyslipidemia exhibit an important clinical relationship because an increase in blood lipids yields an increase in blood pressure (BP. We analyzed the associations of seven polymorphisms of genes involved in lipid metabolism (APOA5 rs3135506, APOB rs1042031, FABP2 rs1799883, LDLR rs5925, LIPC rs1800588, LPL rs328, and MTTP rs1800591 with blood pressure and lipid values in Mexican hypertensive (HT patients. A total of 160 HT patients and 160 normotensive individuals were included. Genotyping was performed through PCR-RFLP, PCR-AIRS, and sequencing. The results showed significant associations in the HT group and HT subgroups classified as normolipemic and hyperlipemic. The alleles FABP2 p.55T, LIPC −514T, and MTTP −493T were associated with elevated systolic BP. Five alleles were associated with lipids. LPL p.474X and FABP2 p.55T were associated with decreased total cholesterol and LDL-C, respectively; APOA5 p.19W with increased HDL-C; APOA5 p.19W and FABP2 p.55T with increased triglycerides; and APOB p.4181K and LDLR c.1959T with decreased triglycerides. The APOB p.E4181K polymorphism increases the risk for HT (OR = 1.85, 95% CI: 1.17–2.93; P=0.001 under the dominant model. These findings indicate that polymorphisms of lipid metabolism genes modify systolic BP and lipid levels and may be important in the development of essential hypertension and dyslipidemia in Mexican HT patients.

  20. Effect of Lipoprotein Lipase Gene Polymorphism on Plasma Lipid Levels, BMI and Subcutaneous Fat Distribution in Simple Obesity Children

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    Objective To study the effects of Hind Ⅲ DNA polymorphis in the lipoprotein lipase ( LPL )gene on plasma lipid levels, body mass index ( BMI) and subcutaneous fat distribution in simple obesity children. Methods The LPL Hind Ⅲ genotypes were detected with the polymerase chain reaction ( PCR ) and restriction fragment length polymorphism ( RFLP ) techniques in 92 children with simple obesity. The levels of the plnsma lipid, plasma lipoproteins, BMI and skinfold thickness in three regions (biceps, subscapular and abdominal uall) were also measured. Results It was shown that the levels of TG, TC, LDL-C, ApoB, BMI, biceps and subscapular skinfold thickness, and the average value of the skinfold thickness in three regions were significantly higher in the obese children uyith H -H- genotype than those with H-+-H- genotype. Conclusions It can be concluded that LPL-Hind Ⅲ polymorphism may modify the levels of plasma lipid, plasma lipoprotein and BMI in children with simple obesity, and meanwhile alters the distribution of subcutaneous fat.

  1. Effect of Lipoprotein Lipase Gene Polymorphism on Plasma Lipid Levels, BMI and Subcutaneous Fat Distribution in Simple Obesity Children

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    Objective To study the effects of Hind Ⅲ DNA polymorphis in the lipoprotein lipase ( LPL )gene on plasma lipid levels, body mass index ( BMI) and subcutaneous fat distribution in simple obesity children. Methods The LPL Hind Ⅲ genotypes were detected with the polymerase chain reaction ( PCR ) and restriction fragment length polymorphism ( RFLP ) techniques in 92 children with simple obesity. The levels of the plnsma lipid, plasma lipoproteins, BMI and skinfold thickness in three regions (biceps, subscapular and abdominal uall) were also measured. Results It was shown that the levels of TG, TC, LDL-C, ApoB, BMI, biceps and subscapular skinfold thickness, and the average value of the skinfold thickness in three regions were significantly higher in the obese children uyith H -H- genotype than those with H-+-H- genotype. Conclusions It can be concluded that LPL-Hind Ⅲ polymorphism may modify the levels of plasma lipid, plasma lipoprotein and BMI in children with simple obesity, and meanwhile alters the distribution of subcutaneous fat.

  2. On the Utter Irrelevance of LPL Graduate Students An Unbiased Survey by Steward Observatory Graduate Students

    CERN Document Server

    Charfman, J J; Eriksen, K A; Knierman, K; Leistra, A; Mamajek, E; Monkiewicz, J; Moustakas, J; Murphy, J; Rigby, J R; Young, P A

    2002-01-01

    We present a new analysis of the irrelevance of Lunar and Planetary Laboratory (LPL) graduate students at the University of Arizona. Based on extensive Monte Carlo simulations we find that the actual number of useful results from LPL graduate students is $0\\pm0.01 (5\\sigma)$. Their irrelevance quotient far surpasses that of string theorists.

  3. A human apoB100 transgenic mouse expresses human apoB100 in the RPE and develops features of early AMD

    DEFF Research Database (Denmark)

    Fujihara, Masashi; Bartels, Emil; Nielsen, Lars B

    2009-01-01

    changes consistent with early human AMD including loss of basal infoldings and accumulation of cytoplasmic vacuoles in the RPE, and basal laminar deposits containing long-spacing collagen and heterogeneous debris in Bruch membrane of apoB100 mice. In apoB100 mice given a high-fat diet, basal linear...

  4. PPARγ regulates expression of carbohydrate sulfotransferase 11 (CHST11/C4ST1, a regulator of LPL cell surface binding.

    Directory of Open Access Journals (Sweden)

    Ismayil Tasdelen

    Full Text Available The transcription factor PPARγ is the key regulator of adipocyte differentiation, function and maintenance, and the cellular target of the insulin-sensitizing thiazolidinediones. Identification and functional characterization of genes regulated by PPARγ will therefore lead to a better understanding of adipocyte biology and may also contribute to the development of new anti-diabetic drugs. Here, we report carbohydrate sulfotransferase 11 (Chst11/C4st1 as a novel PPARγ target gene. Chst11 can sulphate chondroitin, a major glycosaminoglycan involved in development and disease. The Chst11 gene contains two functional intronic PPARγ binding sites, and is up-regulated at the mRNA and protein level during 3T3-L1 adipogenesis. Chst11 knockdown reduced intracellular lipid accumulation in mature adipocytes, which is due to a lowered activity of lipoprotein lipase, which may associate with the adipocyte cell surface through Chst11-mediated sulfation of chondroitin, rather than impaired adipogenesis. Besides directly inducing Lpl expression, PPARγ may therefore control lipid accumulation by elevating the levels of Chst11-mediated proteoglycan sulfation and thereby increasing the binding capacity for Lpl on the adipocyte cell surface.

  5. 猪肌肉组织MDH和LPL基因表达与肌内脂肪含量和脂肪酸组成关系的研究%The Gene Expression of MDH and LPL in Muscle and Their Association with Content of Intramuscular Fat and Composition of Fatty Acids in Pigs

    Institute of Scientific and Technical Information of China (English)

    祝仁铸; 尹逊河; 王元虎; 李少青; 武道留; 王倩

    2013-01-01

    为了研究野莱F1代猪肌内苹果酸脱氢酶(Malate dehydrogenase,MDH)和脂蛋白脂酶(Lipoprotein lipase,LPL)基因表达与肌内脂肪含量及脂肪酸组成的关系,探讨肌内脂肪的沉积机理.本研究以长白山野猪与莱芜猪的杂交1代猪(简称野莱F1代猪)和长×大白猪(各40头,公母各半)为研究对象,在20、35、50、70、90 kg 5个体重阶段采取背腰最长肌,利用荧光定量RT-PCR方法研究MDH和LPL基因表达的发育性变化,分析该变化与肌内脂肪含量和脂肪酸组成的关系.结果表明:随着体重的增加,野莱F1猪和长×大白猪肌内MDH基因表达在20~70 kg阶段呈上升趋势,在70~90 kg阶段呈下降趋势;野菜F1猪和长×大白猪肌内LPL基因表达皆呈持续上升的趋势.相关分析表明:野莱F1猪MDH和LPL mRNA表达均与肌内脂肪含量呈显著正相关(P<0.05),与多不饱和脂肪酸/饱和脂肪酸的比值(PUFA/SFA)不相关(P>0.05);长×大白猪MDH和LPL mRNA表达分别与肌内脂肪含量不相关和显著正相关(P>0.05和P<0.05),分别与PUFA/SFA呈极显著和显著负相关(P<0.01和P<0.05);2种猪肌内PUFA/SFA与肌内脂肪含量皆呈显著负相关(P<0.05).结果提示:猪肌内MDH和LPL基因表达皆具有明显的体重发育特征;可以通过控制猪饲料中PUFA的含量来调节猪肉中PUFA的含量,从而影响MDH和LPL的基因表达,达到调节肌内脂肪含量的目的.

  6. Additive effects of LPL, APOA5 and APOE variant combinations on triglyceride levels and hypertriglyceridemia: results of the ICARIA genetic sub-study

    Science.gov (United States)

    2010-01-01

    Background Hypertriglyceridemia (HTG) is a well-established independent risk factor for cardiovascular disease and the influence of several genetic variants in genes related with triglyceride (TG) metabolism has been described, including LPL, APOA5 and APOE. The combined analysis of these polymorphisms could produce clinically meaningful complementary information. Methods A subgroup of the ICARIA study comprising 1825 Spanish subjects (80% men, mean age 36 years) was genotyped for the LPL-HindIII (rs320), S447X (rs328), D9N (rs1801177) and N291S (rs268) polymorphisms, the APOA5-S19W (rs3135506) and -1131T/C (rs662799) variants, and the APOE polymorphism (rs429358; rs7412) using PCR and restriction analysis and TaqMan assays. We used regression analyses to examine their combined effects on TG levels (with the log-transformed variable) and the association of variant combinations with TG levels and hypertriglyceridemia (TG ≥ 1.69 mmol/L), including the covariates: gender, age, waist circumference, blood glucose, blood pressure, smoking and alcohol consumption. Results We found a significant lowering effect of the LPL-HindIII and S447X polymorphisms (p hypertriglyceridemia. PMID:20429872

  7. Effects of Glycyrrhizic Acid on Peroxisome Proliferator-Activated Receptor Gamma (PPARγ, Lipoprotein Lipase (LPL, Serum Lipid and HOMA-IR in Rats

    Directory of Open Access Journals (Sweden)

    Chia Yoke Yin

    2010-01-01

    Full Text Available Studies on ligand binding potential of glycyrrhizic acid, a potential agonist to PPARγ, displayed encouraging results in amelioration of metabolic syndrome. The regulation of gene cassettes by PPARγ affects glucose homeostasis, lipid, lipoprotein metabolism and adipogenesis. This study was performed to determine the effects of GA on total PPARγ and LPL expression levels, lipid parameters and HOMA-IR. Oral administration of 100 mg/kg GA for 24 hours resulted in an increase in insulin sensitivity with decreases in blood glucose, serum insulin and HOMA-IR. Improvement in serum lipid parameters was also observed with a decrease in triacylglycerol, total cholesterol and LDL-cholesterol and an elevation in HDL-cholesterol. GA administration also resulted in up-regulation of total PPARγ and LPL expression levels in the visceral and subcutaneous adipose tissues, abdominal and quadriceps femoris muscles, as well as liver and kidney, with a significant up-regulation only in the visceral adipose tissue, abdominal and quadriceps femoris muscles. Thus, oral administration of 100 mg/kg GA for 24 hours improved insulin sensitivity and lipid profiles and induced upregulation of total PPARγ and LPL expression levels in all studied tissues.

  8. Lipoprotein Lipase (LPL) Polymorphism and the Risk of Coronary Artery Disease: A Meta-Analysis

    Science.gov (United States)

    Xie, Li; Li, You-Mei

    2017-01-01

    Background: In recent years, the lipoprotein lipase (LPL) polymorphism has been extensively investigated as a potential risk factor for coronary artery disease (CAD). However, the results of these studies have been inconsistent. Therefore, we performed this meta-analysis to explore the association between LPL polymorphism and CAD risk. Methods: The literature was searched from electronic databases such as Embase, China Biological Medicine Database, PubMed, Knowledge Infrastructure, and China National Web of Science by the key words “coronary artery disease”, “lipoprotein lipase” and “polymorphism”. All of the studies included in this manuscript met the inclusion and exclusion criteria. An odds ratio (OR) analysis using a 95% confidence interval (CI) was employed to assess the association of the LPL polymorphism with CAD susceptibility. Results: We performed a meta-analysis of 14 case-control studies including HindIII, Ser447X and PvuII polymorphism. A statistically significant increase in the risk of CAD was associated with LPL HindIII polymorphism. This included HindIII H+H+ genotype (OR = 1.28, 95% CI = 1.09–1.49, p = 0.002, I2 = 43%) and H+ allele genotype (OR = 1.27, 95% CI = 1.03–1.58, p = 0.03, I2 = 67%). Ser447X XX genotype (OR = 2.37, 95% CI = 1.33–4.24, p = 0.004, I2 = 53%) was also associated with CAD risk. However, PvuII polymorphism was found to have no significant association with CAD risk. Conclusions: LPL HindIII polymorphism was significantly associated with the risk of CAD. For Ser447X polymorphism, it was found that only XX genotype was significantly associated with CAD risk. Furthermore, PvuII polymorphism had no significant association with CAD risk. It was considered that LPL HindIII polymorphism might serve as a potential biomarker for CAD risk.

  9. Superiority of the Lunar and Planetary Laboratory (LPL) over Steward Observatory (SO) at the University of Arizona

    OpenAIRE

    2002-01-01

    LPL dominance over Steward is demonstrated through several lines of evidence including observations and modelling of previous April Fools day behavior. The decrease in Steward coolness is attributed to the departure of interesting graduate students from Steward that enrolled at LPL.

  10. The regulation of HSL and LPL expression by DHT and flutamide in human subcutaneous adipose tissue.

    Science.gov (United States)

    Anderson, L A; McTernan, P G; Harte, A L; Barnett, A H; Kumar, S

    2002-05-01

    Clinical observations suggest a role for testosterone in the accumulation of central adiposity and with an associated increased risk of disease. To date, no human study has analysed the role of dihydrotestosterone (DHT) on adipose tissue mass regulation in vitro. This study investigated the role of DHT and androgen receptors (AR) in the regulation of lipolysis and lipogenesis by examining the key enzymes hormone sensitive lipase (HSL) and lipoprotein lipase (LPL) respectively. Isolated abdominal subcutaneous adipocytes (Scad) (n = 15) were treated with either DHT (10(-7)-10(-9) m), an antiandrogen, flutamide (FLT: 10(-7)-10(-9) m) or a combination of DHT (10(-7)-10(-9) m) with FLT (10(-8) m). Relative protein expression of HSL, LPL and AR was determined. In Scad, DHT inhibited HSL expression maximally at 10(-9) m (0.7 +/- 0.4**; p DHT10(-9) m (2.22 +/- 0.48*; p DHT + FLT compared with DHT alone. Androgen receptor expression studies showed an inverse correlation with DHT, whereas DHT + FLT reduced AR expression. These studies indicate that DHT may alter HSL and LPL expression, whereas only LPL expression appears mediated by AR. These findings suggest a physiological role for DHT in the control of adipose tissue mass in women, and indicate that androgens may also play an important role in regulating lipid metabolism.

  11. Cloning and sequence analysis of hepatic lipase (HL) and liportein lipase (LPL) gene in Orange-Spotted Grouper (Epinephelus coioides)%斜带石斑鱼肝脂酶和脂蛋白脂酶基因克隆与序列分析

    Institute of Scientific and Technical Information of China (English)

    胡永乐; 梁旭方; 李观贵; 王琳; 黄志东

    2010-01-01

    为从分子水平研究海水鱼类肝脂酶(hepatic lipase,HL)和脂蛋白脂酶(liportein lipase,LPL)基因在脂质代谢过程中的作用及其分子系统进化地位,采用RT-PCR及RACE法从斜带石斑鱼(Epinephelus coioides)肝脏克隆得到HL、LPL基因cDNA全序列.克隆获得斜带石斑鱼肝脏HL基因cDNA全长2 261 bp,其中5′非翻译区(5′-UTR)为186 bp,3′-UTR为590 bp,开放阅读框(ORF)为1 485 bp,编码494个氨基酸;LPL基因cDNA全长2 191 bp,其中5′-UTR为 144 bp,3′-UTR为 499 bp,ORF为1 548 bp,编码515个氨基酸.序列同源性分析表明,斜带石斑鱼HL、LPL基因与哺乳动物同源性均低于真骨鱼类罗非鱼、斑鳢和真鲷等,这与其亲缘远近关系相一致,表明HL、LPL在进化过程中都相对保守.构建系统发生树显示,斜带石斑鱼HL、LPL基因氨基酸序列与大口黑鲈、真鲷等共同占据进化树上独立的分枝,与较为原始的硬骨鱼类中华鲟在进化树上距离较远.本实验对斜带石斑鱼HL、LPL基因同源性、系统进化地位的研究,为进一步研究海水鱼类脂代谢调控机制,预防鱼类脂代谢疾病奠定了基础.

  12. A transposable element insertion in APOB causes cholesterol deficiency in Holstein cattle.

    Science.gov (United States)

    Menzi, F; Besuchet-Schmutz, N; Fragnière, M; Hofstetter, S; Jagannathan, V; Mock, T; Raemy, A; Studer, E; Mehinagic, K; Regenscheit, N; Meylan, M; Schmitz-Hsu, F; Drögemüller, C

    2016-04-01

    Cholesterol deficiency, a new autosomal recessive inherited genetic defect in Holstein cattle, has been recently reported to have an influence on the rearing success of calves. The affected animals show unresponsive diarrhea accompanied by hypocholesterolemia and usually die within the first weeks or months of life. Here, we show that whole genome sequencing combined with the knowledge about the pedigree and inbreeding status of a livestock population facilitates the identification of the causative mutation. We resequenced the entire genomes of an affected calf and a healthy partially inbred male carrying one copy of the critical 2.24-Mb chromosome 11 segment in its ancestral state and one copy of the same segment with the cholesterol deficiency mutation. We detected a single structural variant, homozygous in the affected case and heterozygous in the non-affected carrier male. The genetic makeup of this key animal provides extremely strong support for the causality of this mutation. The mutation represents a 1.3kb insertion of a transposable LTR element (ERV2-1) in the coding sequence of the APOB gene, which leads to truncated transcripts and aberrant splicing. This finding was further supported by RNA sequencing of the liver transcriptome of an affected calf. The encoded apolipoprotein B is an essential apolipoprotein on chylomicrons and low-density lipoproteins, and therefore, the mutation represents a loss of function mutation similar to autosomal recessive inherited familial hypobetalipoproteinemia-1 (FHBL1) in humans. Our findings provide a direct gene test to improve selection against this deleterious mutation in Holstein cattle.

  13. Impact of phosphatidylcholine liposomes on the compositional changes of VLDL during lipoprotein lipase (LPL)-mediated lipolysis.

    Science.gov (United States)

    Ćwiklińska, Agnieszka; Gliwińska, Anna; Senderowska, Zuzanna; Kortas-Stempak, Barbara; Kuchta, Agnieszka; Dąbkowski, Kamil; Jankowski, Maciej

    2016-02-01

    Lipoprotein lipase (LPL)-mediated triacylglycerol (TAG) hydrolysis in very low density lipoprotein (VLDL) is accompanied by the release of surface material containing phospholipids (PL), free cholesterol (FC) and apolipoproteins, E (apoE) and Cs (apoCII, apoCIII). The released molecules are accepted by high density lipoprotein (HDL), and new HDL-sized apoE-containing particles are also generated. A decrease in the number of HDL particles or abnormalities in their structure is associated with unfavourable changes in the features of VLDL remnants. Phosphatidylcholine liposomes (PC-L) can also act as acceptors of surface material components released from lipoproteins. Thus, the aim of this study was to assess the impact of liposomes on compositional changes of VLDL during its LPL-mediated lipolysis. VLDL isolated from human sera was incubated with LPL (LPL:VLDLTAG; 24 μg/ml:90 mg/dl) and/or PC-L (VLDLPL:PC-LPL; 1:30 weight ratio). After incubation (2h, 37 °C) VLDL was separated from other reaction products, and VLDL lipid and apolipoprotein content were analysed. Newly generated HDL-sized apoE-containing lipoproteins were separated by two-dimensional non-denaturing gradient gel electrophoresis (2D-PAGGE). The reaction of VLDL with PC-L in the presence or absence of LPL significantly affected the VLDL composition. The ratio of core (TAG+cholesteryl ester) to surface (PL+FC) lipids in VLDL decreased 1.8-fold with PC-L, 1.2-fold with LPL and 3-fold with PC-L+LPL. The reaction with PC-L and PC-L+LPL caused a 3.7-fold and 3.2-fold decrease of apoCs/apoE average weight ratio, respectively. Compositional changes in VLDL under the influence of PC-L were accompanied by an increase in the efficiency of VLDL lipolysis and the generation of apoE-containing HDL-sized particles, heterogeneous in size (from ∼ 9 to ∼ 18.8 nm) and mobility (γ and preβ). We conclude that PL-rich particles, similarly to HDL, promote the release of surface material components from VLDL during LPL

  14. Wedelolactone Regulates Lipid Metabolism and Improves Hepatic Steatosis Partly by AMPK Activation and Up-Regulation of Expression of PPARα/LPL and LDLR.

    Directory of Open Access Journals (Sweden)

    Yun Zhao

    Full Text Available Hyperlipidemia is considered one of the greatest risk factors of cardiovascular diseases. We investigated the anti-hyperlipidemic effect and the underlying mechanism of wedelolactone, a plant-derived coumestan, in HepG2 cells and high-fat diet (HFD-induced hyperlipidemic hamsters. We showed that in cultured HepG2 cells, wedelolactone up-regulated protein levels of adenosine monophosphate activated protein kinase (AMPK and peroxisome proliferator-activated receptor-alpha (PPARα as well as the gene expression of AMPK, PPARα, lipoprotein lipase (LPL, and the low-density lipoprotein receptor (LDLR. Meanwhile, administration of wedelolactone for 4 weeks decreased the lipid profiles of plasma and liver in HFD-induced hyperlipidemic hamsters, including total cholesterol (TC, triglycerides (TG, and low-density lipoprotein-cholesterol (LDL-C. The activation of AMPK and up-regulation of PPARα was also observed with wedelolactone treatment. Furthermore, wedelolactone also increased the activities of superoxidase dismutase (SOD and glutathione peroxidase (GSH-Px and decreased the level of the lipid peroxidation product malondialdehyde (MDA in the liver, therefore decreasing the activity of alanine aminotransferase (ALT. In conclusion, we provide novel experimental evidence that wedelolactone possesses lipid-lowering and steatosis-improving effects, and the underlying mechanism is, at least in part, mediated by the activation of AMPK and the up-regulation of PPARα/LPL and LDLR.

  15. Feeding a High Concentrate Diet Down-Regulates Expression of ACACA, LPL and SCD and Modifies Milk Composition in Lactating Goats.

    Directory of Open Access Journals (Sweden)

    Hui Tao

    Full Text Available High concentrate diets are fed to early and mid-lactation stages dairy ruminants to meet the energy demands for high milk production in modern milk industry. The present study evaluated the effects of a high concentrate diet on milk fat and milk composition, especially, cis-9, trans-11 CLA content in milk and gene expression of lactating goats. Eight mid-lactating goats with rumen fistula were randomly assigned into a high concentrate diet (HCD group and low concentrate diet (LCD group. High concentrate diet feeding significantly increased lipopolysaccharides (LPS in plasma and decreased milk fat content, vaccenic acid (VA and cis-9, trans-11 CLA in milk of the lactating goats. The mRNA expression levels of sterol regulatory element binding protein B 1c (SREBP1c, lipoprotein lipase (LPL, fatty acid synthetase (FASN and acetyl-CoA carboxylase α (ACACA, ACCα involving in lipid metabolism were analyzed, and ACACA and LPL all decreased in their expression level in the mammary glands of goats fed a high concentrate diet. DNA methylation rate of stearoyl-CoA desaturase (SCD was elevated and decreased, and SCD mRNA and protein expression was reduced significantly in the mammary glands of goats fed a high concentrate diet. In conclusion, feeding a high concentrate diet to lactating goats decreases milk fat and reduced expression of SCD in the mammary gland, which finally induced cis-9, trans-11 CLA content in milk.

  16. Effect of Low-Power Laser (LPL) and Light-Emitting Diode (LED) on Inflammatory Response in Burn Wound Healing.

    Science.gov (United States)

    Silveira, Paulo C L; Ferreira, Karina B; da Rocha, Franciani R; Pieri, Bruno L S; Pedroso, Giulia S; De Souza, Claudio T; Nesi, Renata T; Pinho, Ricardo A

    2016-08-01

    The aim of the study was to investigate the biochemical and molecular changes in the process of epidermal healing of burn injuries after therapeutic treatment with low-power laser (LPL) and light-emitting diode (LED). Rats were divided into six groups: skin without injury (Sham), burn wounds (BWs), BW + 660-nm LPL, BW + 904-nm LPL, BW + 632-nm LED, and BW + 850-nm LED. The burn wound model was performed using a 100 °C copper plate, with 10 s of contact in the skin. The irradiations started 24 h after the lesion and were performed daily for 7 days. The burn wound groups showed an increase in the superoxide production, dichlorofluorescein, nitrites, and high protein oxidative damage. The activities of glutathione peroxidase and catalase were also increased, and a significant reduction in glutathione levels was observed compared to the control group. However, treatments with 660-nm LPL and 850-nm LED promoted protection against to oxidative stress, and similar results were also observed in the IL-6 and pERK1/2 expression. Taken together, these results suggest that LPL 660 nm and LED 850 nm appear reduced in the inflammatory response and oxidative stress parameters, thus decreasing dermal necrosis and increasing granulation tissue formation, in fact accelerating the repair of burn wounds.

  17. Analyses of non-synonymous obesity risk alleles in SH2B1 (rs7498665) and APOB48R (rs180743) in obese children and adolescents undergoing a 1-year lifestyle intervention.

    Science.gov (United States)

    Volckmar, A-L; Pütter, C; Song, J-Y; Graniger, J; Knoll, N; Wolters, B; Hebebrand, J; Scherag, A; Reinehr, T; Hinney, A

    2013-06-01

    Association of obesity risk alleles of single nucleotide polymorphisms (SNPs) near or in the SH2B adaptor protein 1 gene (SH2B1) and increased body mass index (BMI) has been often described. A gene in close proximity, apolipoprotein B48 receptor gene (APOB48R), is tagged by the same SNP(s).We analyzed 454 overweight and obese children and adolescents (10.8±2.6 years, BMI-SDS 2.4±0.5; 55% girls) who completed a 1-year lifestyle intervention ('Obeldicks' program). Carriers of obesity risk alleles of non-synonymous SNPs in SH2B1 (rs7498665, Thr484Ala) or APOB48R (rs180743, Pro419Ala), as genotyped by TaqMan, were analysed for changes in anthropometrics (body-mass index (BMI), and standardized BMI (BMI-SDS)), blood pressure (systolic and diastolic) and plasma parameters (total cholesterol, LDL-cholesterol, HDL-cholesterol, triacylglycerides, glucose, insulin, and HOMA).We observed no evidence for an association of the obesity risk alleles to alterations in any of the analyzed phenotypes. Both mean BMI and BMI-SDS improved during the intervention independent of genotype. The mean systolic blood pressure was lowered and concentrations of HDL-cholesterol increased significantly.The obesity risk alleles of non-synonymous SNPs at SH2B1 and APOB48R have no strong effect on weight loss-related phenotypes in overweight children after a 1-year lifestyle intervention.

  18. Intestinal SR-BI is upregulated in insulin-resistant states and is associated with overproduction of intestinal apoB48-containing lipoproteins.

    Science.gov (United States)

    Hayashi, Amanda A; Webb, Jennifer; Choi, Joanna; Baker, Chris; Lino, Marsel; Trigatti, Bernardo; Trajcevski, Karin E; Hawke, Thomas J; Adeli, Khosrow

    2011-08-01

    Intestinal lipid dysregulation is a common feature of insulin-resistant states. The present study investigated alterations in gene expression of key proteins involved in the active absorption of dietary fat and cholesterol in response to development of insulin resistance. Studies were conducted in two diet-induced animal models of insulin resistance: fructose-fed hamster and high-fat-fed mouse. Changes in the mRNA abundance of lipid transporters, adenosine triphosphate cassette (ABC) G5, ABCG8, FA-CoA ligase fatty acid translocase P4, Niemann-Pick C1-Like1 (NPC1L1), fatty acid transport protein 4 (FATP4), and Scavenger Receptor Class B Type I (SR-BI), were assessed in intestinal fragments (duodenum, jejunum, and ileum) using quantitative real-time PCR. Of all the transporters evaluated, SR-B1 showed the most significant changes in both animal models examined. A marked stimulation of SR-B1 expression was observed in all intestinal segments examined in both insulin-resistant animal models. The link between SR-BI expression and intestinal lipoprotein production was then examined in the Caco-2 cell model. SR-B1 overexpression in Caco-2 cells increased apolipoprotein B (apoB) 100 and apoB48 secretion, whereas RNAi knock down of SR-B1 decreased secretion of both apoB100 and apoB48. We also observed changes in subcellular distribution of SR-B1 in response to exogenous lipid and insulin. Confocal microscopy revealed marked changes in SR-BI subcellular distribution in response to both exogenous lipids (oleate) and insulin. In summary, marked stimulation of intestinal SR-BI occurs in vivo in animal models of diet-induced insulin resistance, and modulation of SR-BI in vitro regulates production of apoB-containing lipoprotein particles. We postulate that apical and/or basolateral SR-BI may play an important role in intestinal chylomicron production and may contribute to chylomicron overproduction normally observed in insulin-resistant states.

  19. Study of the 3'-ApoB minisatellite performed by PCR in the population of Catalonia (northeast Spain).

    Science.gov (United States)

    Gené, M; Huguet, E; Sánchez-García, C; Moreno, P; Corbella, J; Mezquita, J

    1995-01-01

    Allele and genotype frequencies for the 3'-ApoB locus were determined in a population sample from Catalonia (northeast Spain) using PCR amplification and nonradioactive detection. In a total of 308 unrelated individuals, 16 alleles and 50 genotypes were observed. The 3'-ApoB locus demonstrated a heterozygosity of 80%. The distribution of genotypes is in agreement with expected values according to the Hardy-Weinberg equilibrium.

  20. COMPUTATIONAL MODELING AND DRUG DESIGNING OF LIPOPROTEIN LIPASE (LPL INVOLVED IN ISCHEMIC STROKE

    Directory of Open Access Journals (Sweden)

    Maryam Torabizadeh

    2012-12-01

    Full Text Available Homology modeling and flexible docking of Lipoprotein Lipase has been studied in silico approach. Blast result was found to have similarity with Lipoprotein Lipase of 83% identity with 1LPA. Active site of LPL protein was identified by CASTP. Large potential drugs were designed for identifying molecules that can likely bind to protein target of interest. The different drug derivatives designed were used for docking with the generated structure, among the 10 derivatives designed, 3rd derivative showed highest docking result. The drug derivatives were docked to the protein by hydrogen bonding interactions and these interactions play an important role in the binding studies. Our investigations may be helpful for further studies.

  1. Production of a plant-derived immunogenic protein targeting ApoB100 and CETP: toward a plant-based atherosclerosis vaccine.

    Science.gov (United States)

    Salazar-Gonzalez, Jorge Alberto; Rosales-Mendoza, Sergio; Romero-Maldonado, Andrea; Monreal-Escalante, Elizabeth; Uresti-Rivera, Edith Elena; Bañuelos-Hernández, Bernardo

    2014-12-01

    In an effort to initiate the development of a plant-based vaccination model against atherosclerosis, a cholera toxin B subunit (CTB)-based chimeric protein was designed to target both ApoB100 and CETP epitopes associated with immunotherapeutic effects in atherosclerosis. Epitopes were fused at the C-terminus of CTB to yield a protein called CTB:p210:CETPe. A synthetic gene coding for CTB:p210:CETPe was successfully transferred to tobacco plants with no phenotypic alterations. Plant-derived CTB:p210:CETPe was expressed and assembled in the pentameric form. This protein retained the target antigenic determinants, as revealed by GM1-ELISA and Western blot analyses. Higher expresser lines reached recombinant protein accumulation levels up to 10 µg/g fresh weight in leaf tissues and these lines carry a single insertion of the transgene as determined by qPCR. Moreover, when subcutaneously administered, the biomass from these CTB:p210:CETPe-producing plants was able to elicit humoral responses in mice against both ApoB100 and CETP epitopes and human serum proteins. These findings evidenced for the first time that atherosclerosis-related epitopes can be expressed in plants retaining immunogenicity, which opens a new path in the molecular farming field for the development of vaccines against atherosclerosis.

  2. Lipoprotein Lipase, Tissue Expression and Effects on Genes Related to Fatty Acid Synthesis in Goat Mammary Epithelial Cells

    Directory of Open Access Journals (Sweden)

    Wang-Sheng Zhao

    2014-12-01

    Full Text Available Lipoprotein lipase (LPL serves as a central factor in hydrolysis of triacylglycerol and uptake of free fatty acids from the plasma. However, there are limited data concerning the action of LPL on the regulation of milk fat synthesis in goat mammary gland. In this investigation, we describe the cloning and sequencing of the LPL gene from Xinong Saanen dairy goat mammary gland, along with a study of its phylogenetic relationships. Sequence analysis showed that goat LPL shares similarities with other species including sheep, bovine, human and mouse. LPL mRNA expression in various tissues determined by RT-qPCR revealed the highest expression in white adipose tissue, with lower expression in heart, lung, spleen, rumen, small intestine, mammary gland, and kidney. Expression was almost undetectable in liver and muscle. The expression profiles of LPL gene in mammary gland at early, peak, mid, late lactation, and the dry period were also measured. Compared with the dry period, LPL mRNA expression was markedly greater at early lactation. However, compared with early lactation, the expression was lower at peak lactation and mid lactation. Despite those differences, LPL mRNA expression was still greater at peak, mid, and late lactation compared with the dry period. Using goat mammary epithelial cells (GMEC, the in vitro knockdown of LPL via shRNA or with Orlistat resulted in a similar degree of down-regulation of LPL (respectively. Furthermore, knockdown of LPL was associated with reduced mRNA expression of SREBF1, FASN, LIPE and PPARG but greater expression of FFAR3. There was no effect on ACACA expression. Orlistat decreased expression of LIPE, FASN, ACACA, and PPARG, and increased FFAR3 and SREBF1 expression. The pattern of LPL expression was similar to the changes in milk fat percentage in lactating goats. Taken together, results suggest that LPL may play a crucial role in fatty acid synthesis.

  3. Lipoprotein Lipase, Tissue Expression and Effects on Genes Related to Fatty Acid Synthesis in Goat Mammary Epithelial Cells

    Science.gov (United States)

    Zhao, Wang-Sheng; Hu, Shi-Liang; Yu, Kang; Wang, Hui; Wang, Wei; Loor, Juan; Luo, Jun

    2014-01-01

    Lipoprotein lipase (LPL) serves as a central factor in hydrolysis of triacylglycerol and uptake of free fatty acids from the plasma. However, there are limited data concerning the action of LPL on the regulation of milk fat synthesis in goat mammary gland. In this investigation, we describe the cloning and sequencing of the LPL gene from Xinong Saanen dairy goat mammary gland, along with a study of its phylogenetic relationships. Sequence analysis showed that goat LPL shares similarities with other species including sheep, bovine, human and mouse. LPL mRNA expression in various tissues determined by RT-qPCR revealed the highest expression in white adipose tissue, with lower expression in heart, lung, spleen, rumen, small intestine, mammary gland, and kidney. Expression was almost undetectable in liver and muscle. The expression profiles of LPL gene in mammary gland at early, peak, mid, late lactation, and the dry period were also measured. Compared with the dry period, LPL mRNA expression was markedly greater at early lactation. However, compared with early lactation, the expression was lower at peak lactation and mid lactation. Despite those differences, LPL mRNA expression was still greater at peak, mid, and late lactation compared with the dry period. Using goat mammary epithelial cells (GMEC), the in vitro knockdown of LPL via shRNA or with Orlistat resulted in a similar degree of down-regulation of LPL (respectively). Furthermore, knockdown of LPL was associated with reduced mRNA expression of SREBF1, FASN, LIPE and PPARG but greater expression of FFAR3. There was no effect on ACACA expression. Orlistat decreased expression of LIPE, FASN, ACACA, and PPARG, and increased FFAR3 and SREBF1 expression. The pattern of LPL expression was similar to the changes in milk fat percentage in lactating goats. Taken together, results suggest that LPL may play a crucial role in fatty acid synthesis. PMID:25501331

  4. ApoB100-LDL acts as a metabolic signal from liver to peripheral fat causing inhibition of lipolysis in adipocytes.

    Directory of Open Access Journals (Sweden)

    Josefin Skogsberg

    Full Text Available BACKGROUND: Free fatty acids released from adipose tissue affect the synthesis of apolipoprotein B-containing lipoproteins and glucose metabolism in the liver. Whether there also exists a reciprocal metabolic arm affecting energy metabolism in white adipose tissue is unknown. METHODS AND FINDINGS: We investigated the effects of apoB-containing lipoproteins on catecholamine-induced lipolysis in adipocytes from subcutaneous fat cells of obese but otherwise healthy men, fat pads from mice with plasma lipoproteins containing high or intermediate levels of apoB100 or no apoB100, primary cultured adipocytes, and 3T3-L1 cells. In subcutaneous fat cells, the rate of lipolysis was inversely related to plasma apoB levels. In human primary adipocytes, LDL inhibited lipolysis in a concentration-dependent fashion. In contrast, VLDL had no effect. Lipolysis was increased in fat pads from mice lacking plasma apoB100, reduced in apoB100-only mice, and intermediate in wild-type mice. Mice lacking apoB100 also had higher oxygen consumption and lipid oxidation. In 3T3-L1 cells, apoB100-containing lipoproteins inhibited lipolysis in a dose-dependent fashion, but lipoproteins containing apoB48 had no effect. ApoB100-LDL mediated inhibition of lipolysis was abolished in fat pads of mice deficient in the LDL receptor (Ldlr(-/-Apob(100/100. CONCLUSIONS: Our results show that the binding of apoB100-LDL to adipocytes via the LDL receptor inhibits intracellular noradrenaline-induced lipolysis in adipocytes. Thus, apoB100-LDL is a novel signaling molecule from the liver to peripheral fat deposits that may be an important link between atherogenic dyslipidemias and facets of the metabolic syndrome.

  5. Lipoprotein lipase gene variants: Association with acute myocardial ...

    African Journals Online (AJOL)

    Lipoprotein lipase gene variants: Association with acute myocardial infarction and lipid profiles. ... Therefore, genes involved in lipid and lipoprotein metabolism pathways such as lipoprotein lipase (LPL), are proper candidates ... Article Metrics.

  6. LPL-01 utilizando vías diferentes de exposición

    Directory of Open Access Journals (Sweden)

    A Mancebo

    2005-01-01

    Full Text Available Los nemátodos parásitos de las plantas, conocidos como plagas agrícolas desde el siglo XIX, causan un 9% de pérdidas de cultivos en los países desarrollados y un 14% en los países en desarrollo. El Paecilomyces lilacinus es un hongo parásito que ataca formas sedentarias de los nemátodos, como los huevos. Su valoración como agente microbiano de control debe incluir una evaluación de su virulencia hacia organismos no-diana, tomando en consideración las vías posibles de exposición de los humanos. Para evaluar la patogenicidad de la cepa LPL-01 del P. lilacinus en ratas, se administró por las vías oral, pulmonar e intravenosa. Las observaciones clínicas fueron diarias, y se evaluó el comportamiento del peso corporal. Se estimó el aclaramiento mediante recolección de las heces fecales y análisis de muestras de los pulmones y de la sangre, según la vía de administración, y se evaluó la infectividad mediante toma de muestras de órganos de animales inoculados sacrificados a intervalos. Durante estos sacrificios, y al final de los ensayos, se realizó la necropsia de los animales. No ocurrieron mortalidades, ni evidencias de patogenicidad relacionada con el tratamiento en los ensayos oral y pulmonar, no provocando el hongo una infestación significativa. Por vía endovenosa, el microorganismo provocó alteraciones anátomo-patológicas en hígado y bazo, coincidiendo con el período de máxima infestación. Se concluyó que la cepa LPL-01 del P. lilacinus, a las dosis evaluadas, no es patogénica por las vías oral y pulmonar, siendo levemente patogénica por vía endovenosa

  7. Monoclonal Antibodies That Bind to the Ly6 Domain of GPIHBP1 Abolish the Binding of LPL

    DEFF Research Database (Denmark)

    Hu, Xuchen; Sleeman, Mark W; Miyashita, Kazuya

    2017-01-01

    GPIHBP1, an endothelial cell protein, binds lipoprotein lipase (LPL) in the interstitial spaces and shuttles it to its site of action inside blood vessels. For years, studies of human GPIHBP1 have been hampered by an absence of useful antibodies. We reasoned that monoclonal antibodies (mAbs) agai......GPIHBP1, an endothelial cell protein, binds lipoprotein lipase (LPL) in the interstitial spaces and shuttles it to its site of action inside blood vessels. For years, studies of human GPIHBP1 have been hampered by an absence of useful antibodies. We reasoned that monoclonal antibodies (m......, we report the development of a panel of human GPIHBP1-specific mAbs. Two mAbs against GPIHBP1's Ly6 domain, RE3 and RG3, abolished LPL binding, while an antibody against the acidic domain, RF4, did not. Also, mAbs RE3 and RG3 bound with reduced affinity to a mutant GPIHBP1 containing an Ly6 domain...

  8. Effects of insulin resistance and hepatic lipid accumulation on hepatic mRNA expression levels of apoB, MTP and L-FABP in non-alcoholic fatty liver disease.

    Science.gov (United States)

    Higuchi, Nobito; Kato, Masaki; Tanaka, Masatake; Miyazaki, Masayuki; Takao, Shinichiro; Kohjima, Motoyuki; Kotoh, Kazuhiro; Enjoji, Munechika; Nakamuta, Makoto; Takayanagi, Ryoichi

    2011-11-01

    Non-alcoholic fatty liver disease (NAFLD) is considered a hepatic manifestation of metabolic syndrome, which is known to be associated with insulin resistance (IR). NAFLD occurs when the rate of hepatic fatty acid uptake from plasma and de novo fatty acid synthesis is greater than the rate of fatty acid oxidation and excretion as very low-density lipoprotein (VLDL). To estimate the effects of IR on hepatic lipid excretion, mRNA expression levels of genes involved in VLDL assembly were analyzed in NAFLD liver. Twenty-two histologically proven NAFLD patients and 10 healthy control subjects were enrolled in this study. mRNA was extracted from liver biopsy samples and real-time PCR was performed to quantify the expression levels of apolipoprotein B (apoB), microsomal triglyceride transfer protein (MTP) and liver fatty-acid binding protein (L-FABP). Hepatic expression levels of the genes were compared between NAFLD patients and control subjects. In NAFLD patients, we also examined correlations between expression levels of the genes and metabolic factors, including IR, and the extent of obesity and hepatic lipid accumulation. Hepatic expression levels of apoB, MTP and L-FABP were significantly up-regulated in NAFLD patients compared to control subjects. The expression levels of MTP were correlated with those of apoB, but not with those of L-FABP. In the NAFLD liver, the expression levels of MTP were significantly reduced in patients with HOMA-IR >2.5. In addition, a significant reduction in MTP expression was observed in livers with advanced steatosis. Enhanced expression of genes involved in VLDL assembly may be promoted to release excess lipid from NAFLD livers. However, the progression of IR and hepatic steatosis may attenuate this compensatory process.

  9. Low density lipoprotein: structure, dynamics, and interactions of apoB-100 with lipids

    DEFF Research Database (Denmark)

    Murtola, T.; Vuorela, T. A.; Hyvonen, M. T.;

    2011-01-01

    Low-density lipoprotein (LDL) transports cholesterol in the bloodstream and plays an important role in the development of cardiovascular diseases, in particular atherosclerosis. Despite its importance to health, the structure of LDL is not known in detail. This is worrying since the lack of LDL......'s structural information makes it more difficult to understand its function. In this work, we have combined experimental and theoretical data to construct LDL models comprised of the apoB-100 protein wrapped around a lipid droplet of about 20 nm in size. The models are considered by near-atomistic multi......-microsecond simulations to unravel structural as well as dynamical properties of LDL, with particular attention paid to lipids and their interactions with the protein. We find that the distribution and the ordering of the lipids in the LDL particle are rather complex. The previously proposed 2- and 3- layer models turn...

  10. Echium Oil Reduces Atherosclerosis in apoB100-only LDLrKO Mice

    Science.gov (United States)

    Forrest, Lolita M.; Boudyguina, Elena; Wilson, Martha D.; Parks, John S.

    2012-01-01

    Introduction The anti-atherogenic and hypotriglyceridemic properties of fish oil are attributed to its enrichment in eicosapentaenoic acid (EPA; 20:5, n-3) and docosahexaenoic acid (DHA; 22:6, n-3). Echium oil contains stearidonic acid (SDA; 18:4, n-3), which is metabolized to EPA in humans and mice, resulting in decreased plasma triglycerides. Objective We used apoB100 only, LDLrKO mice to investigate whether echium oil reduces atherosclerosis. Methods Mice were fed palm, echium, or fish oil-containing diets for 16 weeks and plasma lipids, lipoproteins, and atherosclerosis were measured. Results Compared to palm oil, echium oil feeding resulted in significantly less plasma triglyceride and cholesterol levels, and atherosclerosis, comparable to that of fish oil. Conclusion This is the first report that echium oil is anti-atherogenic, suggesting that it may be a botanical alternative to fish oil for atheroprotection. PMID:22100249

  11. Apolipoprotein B levels, APOB alleles, and risk of ischemic cardiovascular disease in the general population, a review

    DEFF Research Database (Denmark)

    Benn, Marianne

    2009-01-01

    . The present review examines, with focus on general population studies, apolipoprotein B levels as a predictor of ischemic cardiovascular disease, as well as the association of mutations and polymorphisms in APOB with plasma apolipoprotein B levels, and risk of ischemic cardiovascular disease. The studies can......, or ischemic stroke in the general population....

  12. Genetic polymorphism study at four minisatellite loci (D1S80, D17S5, D19S20, and APOB) among five Indian population groups.

    Science.gov (United States)

    Das, Birajalaxmi; Ghosh, Anu; Chauhan, P S; Seshadri, M

    2002-06-01

    The present study reports the genetic variation observed among five anthropologically distinct population groups of India, using four highly polymorphic minisatellite loci (D1S80, D17S5, D19S20, and APOB 3' VNTR) in order to examine the effect of geographical and linguistic affiliations on the genetic affinities among these groups. Random individuals from five ethnic groups were studied; the sample size ranged from 235 to 364. The population groups belong to two geographically separated regions of India, the state of Maharashtra (western India) and the state of Kerala (southern India). The two Maharashtrian groups (Konkanastha Brahmins and Marathas) speak "Marathi," an Indo-European language, whereas the three Kerala population groups (Nairs, Ezhavas, and Muslims) speak "Malayalam," an Indo-Dravidian language. Genomic DNA was extracted from peripheral blood samples and analyzed using amplified fragment length polymorphism (Amp-FLP) technique. All four loci displayed high heterozygosity with average heterozygosity in the range of 0.82 to 0.84. The Polymorphic Information Content and Power of Discrimination were > or = 0.75 and > or = 0.80, respectively. The coefficient of gene differentiation was found to be low (average G(ST) = 1.2%; range between 0.6% at D1S80 locus to 1.6% at APOB 3' VNTR locus) across the loci, indicating close affinity among the population groups. The neighbor-joining tree revealed two clear clusters, one for the two Maharashtrian population groups and the other for the three Kerala population groups. The results obtained are in conformity with the geographical and linguistic backgrounds of the studied populations.

  13. Relationship between common lipoprotein lipase gene sequence variants, hyperinsulinemia, and risk of ischemic heart disease: A population-based study

    DEFF Research Database (Denmark)

    Jeppesen, Jørgen; Hansen, Tine Willum; Torp-Pedersen, Christian;

    2010-01-01

    Hyperinsulinemia and lipoprotein lipase (LPL) are important determinants of fasting and postprandial plasma triglyceride levels. High insulin and high triglyceride levels are associated with an increased risk of ischemic heart disease (IHD). This study aimed to find out whether common LPL gene...

  14. Severe Hypertriglyceridemia due to a novel p.Q240H mutation in the Lipoprotein Lipase gene.

    Science.gov (United States)

    Soto, Angela Ganan; McIntyre, Adam; Agrawal, Sungeeta; Bialo, Shara R; Hegele, Robert A; Boney, Charlotte M

    2015-09-04

    Lipoprotein Lipase (LPL) deficiency is a rare autosomal recessive disorder with a heterogeneous clinical presentation. Several mutations in the LPL gene have been identified to cause decreased activity of the enzyme. An 11-week-old, exclusively breastfed male presented with coffee-ground emesis, melena, xanthomas, lipemia retinalis and chylomicronemia. Genomic DNA analysis identified lipoprotein lipase deficiency due to compound heterozygosity including a novel p.Q240H mutation in exon 5 of the lipoprotein lipase (LPL) gene. His severe hypertriglyceridemia, including xanthomas, resolved with dietary long-chain fat restriction. We describe a novel mutation of the LPL gene causing severe hypertriglyceridemia and report the response to treatment. A review of the current literature regarding LPL deficiency syndrome reveals a few potential new therapies under investigation.

  15. Allelic variants of the genes of apolipoproteins B and CII in patients with coronary heart disease and in healthy individuals from the Moscow population

    Energy Technology Data Exchange (ETDEWEB)

    Pogoda, T.V.; Kolosova, T.V.; Lyudvikova, E.K. [Institute of Molecular Genetics, Moscow (Russian Federation)] [and others

    1995-07-01

    Allelic frequencies of a microsatellite of the apolipoprotein CII gene (APOCII) and a minisatellite of the apolipoprotein B gene (APOB) were studied by using polymerase chain reaction (PCR). The study was conducted on a random sample of male Moscow inhabitants and a sample of patients with coronary heart disease (CHD) from the same population. Fourteen variants of the APOB minisatellite (the 82% heterozygosity level) and 13 alleles of the APOCII microsatellite (the 85% heterozygosity level) were found. CHD patients significantly differed from the control group in the distributions of alleles in these loci: APOB 32, APOB 46, APOB 48, and APOB 50 as well as APOCII 17 and APOCII 29 were found more frequently. A relationship was found between the distributions of APOB and APOCII in the CHD patients. The CHD patients with alleles APOCII 21 and APOCII 30 very often had the allele APOB 32; and patients with the genotype APOB 34, 36 had the allele APOCII 29 even more often than affected individuals in general. Individuals of the control group with the allele APOCII30 exhibited hypertriglyceridemia without increased levels of total cholesterol and apolipoprotein B in plasma. 14 refs., 3 figs., 6 tabs.

  16. Chylomicron and apoB48 metabolism in the JCR:LA corpulent rat, a model for the metabolic syndrome.

    Science.gov (United States)

    Mangat, R; Su, J; Scott, P G; Russell, J C; Vine, D F; Proctor, S D

    2007-06-01

    Postprandial (PP) lipaemia is a significant contributor to the development of dyslipidaemia and cardiovascular disease (CVD). It is also evident that PP lipaemia is prevalent during conditions of obesity and insulin resistance (IR) and may contribute to increased progression of CVD. Our group has assessed the potential of the obese JCR:LA-cp rat as a model of PP lipaemia in order to explore CM (chylomicron) metabolism during the onset and development of IR in the metabolic syndrome. Studies confirm that both fasting plasma and PP apoB48 (apolipoprotein B48) area under the curve are significantly elevated in the obese JCR:LA-cp phenotype as compared with lean controls. Mechanistic studies have also shown that the concentration of lymphatic CM apoB48 and CM size are significantly increased in this model. Furthermore, PP dyslipidaemia in the obese rat can be improved acutely with supplementation of n-3 polyunsaturated fatty acids. Using a different approach, we have subsequently hypothesized that the vascular remodelling that accompanies IR may explain accelerated entrapment of apoB48-containing particles. Small leucine-rich proteoglycans (including biglycan and decorin) have been observed to co-localize with apoB in human tissue. However, the potential impact of IR on vascular remodelling, particularly in the presence of obesity, remains unclear. Preliminary observations from the JCR:LA-cp model indicate that biglycan protein core content increases with age and is exacerbated by IR, suggestive of pro-atherogenic remodelling. The focus of this review is to contribute to the perspective of PP lipaemia in CVD risk associated with the metabolic syndrome through the use of animal models.

  17. The −93T/G LPL Promoter Polymorphism Is Associated with Lower Third-Trimester Plasma Triglycerides in Pregnant African American Women

    Science.gov (United States)

    Schmella, Mandy J.; Ferrell, Robert E.; Gallaher, Marcia J.; Lykins, David R.; Althouse, Andrew D.; Roberts, James M.; Hubel, Carl A.

    2014-01-01

    Background Hypertriglyceridemia is a risk factor for cardiovascular disease and several pregnancy complications. Lipoprotein lipase (LPL) genetic variation modulates nonpregnancy plasma triglycerides, but effects during pregnancy are unknown. The G allele of the LPL −93T/G promoter polymorphism is 16–23 times more prevalent in Blacks than in Whites, contributing to lower triglycerides in nonpregnant African Americans by increasing LPL expression. Purpose This study investigated whether the triglyceride-lowering effect of −93G in African Americans is observed during pregnancy. Methods Genotyping was performed on 124 African American women with uncomplicated pregnancies for common functional LPL polymorphisms/mutations (−93T/G, D9N, N291S, S447X). Third-trimester plasma triglyceride, high- and low-density lipoprotein cholesterol, apolipoprotein B, and free fatty acid concentrations were measured with colorimetric assays. Clinical characteristics and lipid values were compared across the −93T/G genotypes. Results Triglycerides were significantly lower in women with the −93GG compared to the −93TT genotype, both with (n = 124, p = 0.02) and without (n = 108, p = 0.03) inclusion of participants with other LPL variant alleles. Triglyceride differences persisted after adjustment for pre-pregnancy body mass index, gestational age at delivery, and smoking. There were no significant differences in the other lipids or apolipoprotein B by −93T/G genotype. Conclusions Despite the considerable metabolic changes accompanying pregnancy, the triglyceride-lowering effect associated with the −93GG LPL genotype in African Americans persists during late pregnancy. The −93GG genotype might protect against pregnancy complications stemming from hypertriglyceridemia, but the overall increased risk for pregnancy complications in African American women points to complex, multifactorial relationships among risk factors, race, and adverse pregnancy outcomes. PMID:25566792

  18. The -93T/G LPL Promoter Polymorphism Is Associated With Lower Third-Trimester Triglycerides in Pregnant African American Women.

    Science.gov (United States)

    Schmella, Mandy J; Ferrell, Robert E; Gallaher, Marcia J; Lykins, David L; Althouse, Andrew D; Roberts, James M; Hubel, Carl A

    2015-07-01

    Hypertriglyceridemia is a risk factor for cardiovascular disease and several pregnancy complications. Lipoprotein lipase (LPL) genetic variation modulates nonpregnancy plasma triglycerides, but its effects during pregnancy are unknown. The G allele of the LPL -93T/G promoter polymorphism is 16-23 times more prevalent in Blacks than in Whites, contributing to lower triglycerides in nonpregnant African Americans by increasing LPL expression. This study investigated whether the triglyceride-lowering effect of -93G is observed in African Americans during pregnancy. Genotyping was performed on 124 African American women with uncomplicated pregnancies for common functional LPL polymorphisms/mutations (-93T/G, D9N, N291S, and S447X). Third-trimester plasma triglyceride, high- and low-density lipoprotein cholesterol, apolipoprotein B, and free fatty acid concentrations were measured with colorimetric assays. Clinical characteristics and lipid values were compared across the -93T/G genotypes. Triglycerides were significantly lower in women with the -93GG compared to the -93TT genotype, both with (n = 124, p = .02) and without (n = 108, p = .03) inclusion of participants with other LPL variant alleles. Triglyceride differences persisted after adjustment for prepregnancy body mass index, gestational age at delivery, and smoking. There were no significant differences in the other lipids or apolipoprotein B by -93T/G genotype. Despite the considerable metabolic changes accompanying pregnancy, the triglyceride-lowering effect associated with the -93GG LPL genotype in African Americans persists during late pregnancy. The -93GG genotype might protect against pregnancy complications stemming from hypertriglyceridemia, but the overall increased risk of pregnancy complications in African American women points to complex, multifactorial relationships among risk factors, race, and adverse pregnancy outcomes. © The Author(s) 2015.

  19. XbaⅠpolymorphisms of apolipoprotein B gene:Another risk factor of gallstone formation after radical gastrectomy

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    AIM:To prospectively investigate the association between the XbaⅠpolymorphisms of apolipoprotein B (APOB)gene and gallstone formation following gastrectomy.METHODS:The study was conducted between January 2005 and December 2006.A total of 186 gastric cancer patients who had undergone radical gastrectomy were grouped according to XbaⅠpolymorphisms of APOB gene(X+X-group,n=24 and X-X-group,n =162)and compared.The XbaⅠpolymorphisms of APOB gene were detected by polymerase chain reaction-restriction fragment len...

  20. Gene expression and enzyme activity of lipoprotein lipase correlate with intramuscular fat content in Guangxi san-huang and Arbor Acres chickens.

    Science.gov (United States)

    Huang, Y N; Wang, J; Chen, B J; Jiang, Q Y; Guo, Y F; Lan, G Q; Jiang, H S

    2016-01-01

    Lipoprotein lipase (LPL) is a key enzyme in lipid metabolism. This study investigated LPL gene expression, LPL enzyme activity, and the correlation of each with intramuscular fat (IMF) in Chinese Guangxi san-huang (GXSH) and Arbor Acres (AA) chickens. The results showed that age and breed had significant effects on LPL expression and enzyme activity. Correlation analyses showed significant positive correlations between LPL expression levels and IMF contents in the breast and thigh tissues of both GXSH (r = 0.712, P = 0.001; r = 0.792, P < 0.001, respectively) and AA (r = 0.644, P < 0.001; r = 0.545, P < 0.001, respectively) chickens. The results also indicated a significant positive correlation between LPL enzyme activity and IMF contents in the breast and thigh tissues of both GXSH (r = 0.615, P = 0.001; r = 0.685, P < 0.001, respectively) and AA (r = 0.600, P = 0.001; r = 0.528, P = 0.003, respectively) chickens. The results indicated that the LPL gene was significantly correlated with IMF in these two breeds. The results presented here could contribute to knowledge of LPL mRNA developmental expression patterns and enzyme activity, and it could facilitate further research on the molecular mechanisms underlying IMF deposition in chickens.

  1. LPL Announces World's Fastest TFT-LCD Panel for Mobile Phones%LG飞利浦已研制出用于手机的TFT-LCD

    Institute of Scientific and Technical Information of China (English)

    Ken Werner

    2006-01-01

    @@ LG.Philips LCD (LPL) announced at Sept.13th 2006, it has developed the industry's fastest TFT-LCD panel for mobile phones, which will permit next-generation handsets to display TV and video content with less motion blur.

  2. RNA/DNA ratio and LPL and MyoD mRNA expressions in muscle of Oreochromis niloticus fed with elevated levels of palm oil

    Science.gov (United States)

    Ayisi, Christian Larbi; Zhao, Jinliang

    2016-02-01

    Palm oil is of great potential as one of the sustainable alternatives to fish oil (FO) in aquafeeds. In this present study, five isonitrogenous diets (32% crude protein) with elevated palm oil levels of 0%, 2%, 4%, 6% and 8% were used during an 8-week feeding trial to evaluate its effects on RNA/DNA ratio and lipoprotein lipase (LPL) and MyoD mRNA expressions in muscle of Oreochromis niloticus. The results showed that RNA, DNA content as well as ratio of RNA to DNA were significantly affected ( P palm oil level. There was a strong positive correlation between nucleic acid concentration (RNA concentration and RNA: DNA ratio) and specific growth rate (SGR), protein efficiency ratio (PER), while a negative correlation existed between nucleic acid concentration (RNA concentration and RNA: DNA ratio) and feed conversion ratio (FCR). The mRNA expressions of LPL and MyoD in muscle were not significantly affected by the different palm oil levels, although the highest expression was observed in fish fed with 6% palm oil level. There also existed a strong positive correlation between the mRNA expression of LPL, MyoD and SGR, PER, while their correlation with FCR was negative. In conclusion, elevated palm oil affected the RNA, DNA concentration as well as RNA/DNA ratio significantly, although the mRNA expression of LPL and MyoD were not affected significantly by elevated palm oil levels.

  3. T-Cells Specific for a Self-Peptide of ApoB-100 Exacerbate Aortic Atheroma in Murine Atherosclerosis.

    Science.gov (United States)

    Shaw, Michael K; Tse, Kevin Y; Zhao, Xiaoqing; Welch, Kathryn; Eitzman, Daniel T; Thipparthi, Raghavendar R; Montgomery, Paul C; Thummel, Ryan; Tse, Harley Y

    2017-01-01

    On the basis of mouse I-A(b)-binding motifs, two sequences of the murine apolipoprotein B-100 (mApoB-100), mApoB-1003501-3515 (designated P3) and mApoB-100978-992 (designated P6), were found to be immunogenic. In this report, we show that P6 is also atherogenic. Immunization of Apoe(-/-) mice fed a high-fat diet (HFD) with P6 resulted in enhanced development of aortic atheroma as compared to control mice immunized with an irrelevant peptide MOG35-55 or with complete Freund's adjuvant alone. Adoptive transfer of lymph node cells from P6-immunized donor mice to recipients fed an HFD caused exacerbated aortic atheromas, correlating P6-primed cells with disease development. Finally, P6-specific T cell clones were generated and adoptive transfer of T cell clones into recipients fed an HFD led to significant increase in aortic plaque coverage when compared to control animals receiving a MOG35-55-specific T cell line. Recipient mice not fed an HFD, however, did not exhibit such enhancement, indicating that an inflammatory environment facilitated the atherogenic activity of P6-specific T cells. That P6 is identical to or cross-reacts with a naturally processed peptide of ApoB-100 is evidenced by the ability of P6 to stimulate the proliferation of T cells in the lymph node of mice primed by full-length human ApoB-100. By identifying an atherogenic T cell epitope of ApoB-100 and establishing specific T cell clones, our studies open up new and hitherto unavailable avenues to study the nature of atherogenic T cells and their functions in the atherosclerotic disease process.

  4. Targeted Knockdown of Hepatic SOAT2 With Antisense Oligonucleotides Stabilizes Atherosclerotic Plaque in ApoB100-only LDLr-/- Mice.

    Science.gov (United States)

    Melchior, John T; Olson, John D; Kelley, Kathryn L; Wilson, Martha D; Sawyer, Janet K; Link, Kerry M; Rudel, Lawrence L

    2015-09-01

    To test the hypothesis that the attenuation of cholesterol oleate packaging into apoB-containing lipoproteins will arrest progression of pre-existing atherosclerotic lesions. Atherosclerosis was induced in apoB-100 only, LDLr(-/-) mice by feeding a diet enriched in cis-monounsaturated fatty acids for 24 weeks. A subset of mice was then euthanized to quantify the extent of atherosclerosis. The remaining mice were continued on the same diet (controls) or assigned to the following treatments for 16 weeks: (1) a diet enriched in n-3 polyunsaturated fatty acids, (2) the cis-monounsaturated fatty acid diet plus biweekly injections of an antisense oligonucleotide specific to hepatic sterol-O-acyltransferase 2 (SOAT2); or (3) the cis-monounsaturated fatty acid diet and biweekly injections of a nontargeting hepatic antisense oligonucleotide. Extent of atherosclerotic lesions in the aorta was monitored morphometrically in vivo with magnetic resonance imaging and ex vivo histologically and immunochemically. Hepatic knockdown of SOAT2 via antisense oligonucleotide treatment arrested lesion growth and stabilized lesions. Hepatic knockdown of SOAT2 in apoB100-only, LDLr(-/-) mice resulted in remodeling of aortic atherosclerotic lesions into a stable phenotype, suggesting SOAT2 is a viable target for the treatment of atherosclerosis. © 2015 American Heart Association, Inc.

  5. Mucosal tolerance to a combination of ApoB and HSP60 peptides controls plaque progression and stabilizes vulnerable plaque in Apob(tm2SgyLdlr(tm1Her/J mice.

    Directory of Open Access Journals (Sweden)

    Lakshmi Mundkur

    Full Text Available Oral tolerance to auto antigens reduces the development of atherosclerosis in mouse models. However, the effect of immune tolerance to multiple self antigenic peptides in plaque progression and stabilization is not known. We studied the protective effect of mucosal tolerance to peptides from apolipoprotein B (ApoB; 661-680 and heat shock protein 60 (HSP60; 153-163, in combination with diet, in the prevention of atherosclerotic lesion progression and plaque stabilization in ApoB(tm25gyLDLr(tm1Her mice. We found that oral administration of five doses of a combination of ApoB and HSP60 peptides (20 µg/mice/dose induced tolerance to both the peptides and reduced early plaque development by 39.9% better than the individual peptides (ApoB = 28.7%;HSP60 = 26.8%(P<0.001. Oral tolerance to combination of peptides along with diet modification arrested plaque progression by 37.6% which was associated with increases in T-regulatory cell and transforming growth factor-β expression in the plaque and peripheral circulation. Reduced macrophage infiltration and tumor necrosis factor-α expression in the plaque was also observed. Tolerance with continued hypercholesterolemia resulted in 60.8% reduction in necrotic core area suggesting plaque stabilization, which was supported by reduction in apoptosis and increased efferocytosis demonstrated by greater expression of receptor tyrosine kinase Mer (MerTK in the plaque. Tolerance to the two peptides also reduced the expression of matrix metalloproteinase 9, tissue factor, calprotectin, and increased its collagen content. Our study suggests that oral tolerance to ApoB and HSP60 peptide combination induces CD4(+ CTLA4(+ Tregs and CD4(+CD25(+Foxp3(+ Tregs secreting TGF-β, which inhibit pathogenic T cell response to both peptides thus reducing the development and progression of atherosclerosis and provides evidence for plaque stabilization in ApoB(tm25gyLDLr(tm1Her mice.

  6. VLDL hydrolysis by LPL activates PPAR-alpha through generation of unbound fatty acids.

    Science.gov (United States)

    Ruby, Maxwell A; Goldenson, Benjamin; Orasanu, Gabriela; Johnston, Thomas P; Plutzky, Jorge; Krauss, Ronald M

    2010-08-01

    Recent evidence suggests that lipoproteins serve as circulating reservoirs of peroxisomal proliferator activated receptor (PPAR) ligands that are accessible through lipolysis. The present study was conducted to determine the biochemical basis of PPAR-alpha activation by lipolysis products and their contribution to PPAR-alpha function in vivo. PPAR-alpha activation was measured in bovine aortic endothelial cells following treatment with human plasma, VLDL lipolysis products, or oleic acid. While plasma failed to activate PPAR-alpha, oleic acid performed similarly to VLDL lipolysis products. Therefore, fatty acids are likely to be the PPAR-alpha ligands generated by VLDL lipolysis. Indeed, unbound fatty acid concentration determined PPAR-alpha activation regardless of fatty acid source, with PPAR-alpha activation occurring only at unbound fatty acid concentrations that are unachievable under physiological conditions without lipase action. In mice, a synthetic lipase inhibitor (poloxamer-407) attenuated fasting-induced changes in expression of PPAR-alpha target genes. Apolipoprotein CIII (apoCIII), an endogenous inhibitor of lipoprotein and hepatic lipase, regulated access to the lipoprotein pool of PPAR-alpha ligands, because addition of exogenous apoCIII inhibited, and removal of endogenous apoCIII potentiated, lipolytic PPAR-alpha activation. These data suggest that the PPAR-alpha response is generated by unbound fatty acids released locally by lipase activity and not by circulating plasma fatty acids.

  7. Sex-associated effect of CETP and LPL polymorphisms on postprandial lipids in familial hypercholesterolaemia

    Directory of Open Access Journals (Sweden)

    Marvaki Christina

    2009-06-01

    Full Text Available Abstract Background This study assessed the gender-specific influence of the cholesteryl ester transfer protein (TaqIB, I405V and lipoprotein lipase (S447X polymorphisms on the response to an oral fat tolerance test in heterozygotes for familial hypercholesterolaemia. Methods We selected and genotyped 80 men and postmenopausal women heterozygous for familial hypercholesterolaemia (main group as well as 11 healthy control subjects. Patients were subgrouped based on their response to oral fat tolerance test. The oral fat tolerance test was defined as pathological when postprandial triglyceride concentration was higher than the highest triglyceride concentration observed in healthy subjects (220 mg/dl at any time (2, 4, 6 or 8 h. Results In the pathological subgroup, men had significantly higher incremental area under the curve after oral fat tolerance test than postmenopausal women. Furthermore, multivariate analysis revealed a gender association of TaqIB and I405V influence on postprandial lipaemia in this subgroup. Conclusion In conclusion, it seems that gender and TaqIB polymorphism of the cholesteryl ester transfer protein gene were both associated with the distribution of triglyceride values after oral fat tolerance test, only in subjects with a pathological response to oral fat tolerance test. Specifically, men carrying the B2 allele of the TaqIB polymorphism showed a higher postprandial triglyceride peak and a delayed return to basal values compared with women carrying B2. However, further investigations in larger populations are required to replicate and confirm these findings.

  8. ¿La Apoteosis de Heracles o una escena de Apobates? A propósito de una cratera de campana procedente de La Loma del Escorial de Los Nietos (Cartagena, Murcia

    Directory of Open Access Journals (Sweden)

    Rodríguez Pérez, Diana

    2014-12-01

    Full Text Available The aim of this article is to assess the traditional iconographic identification of the obverse of a 4th century Greek bell crater from the Iberian site of La Loma del Escorial de Los Nietos (Cartagena, Murcia. The scene has been identified as an apotheosis of Heracles. Nevertheless, a detailed analysis of its iconography and of a feature neglected in the previous study of the vase by its excavators —the remains of a shield— make it possible to argue in favor of an apobates race instead —the only scene of this type attested in the Iberian Peninsula. I present here an analysis of both iconographic motifs —the apotheosis of Heracles and the apobates race— that will reveal interesting findings on the ways in which images and iconographic types acquire meaning. It also sheds light on the kind of images favored by the receptors of these vases in the Peninsula — the Iberians. An up-to-date catalogue of Attic vases depicting each theme is included.En el presente artículo se revisa la identificación iconográ- fica de la cara A de una cratera griega fragmentaria del siglo IV a.C. procedente del yacimiento ibérico de La Loma del Escorial de Los Nietos (Cartagena, Murcia. La escena se ha identificado tradicionalmente como la apoteosis de Heracles, no obstante, tras un análisis detallado de la misma, en particular del resto de un escudo previamente inadvertido que porta el personaje principal, creemos que la iconografía se corresponde con la del apobates victorioso, un unicum en la Península Ibérica. Presentamos un análisis de ambos motivos iconográficos que revelará interesantes conclusiones sobre el funcionamiento de los tipos iconográficos y mecanismos de creación de significado en la pintura de vasos de la época, así como sobre el tipo de imágenes estimadas por los receptores de esas piezas en la Península Ibérica, los íberos. Se incluye también un catálogo actualizado de los vasos áticos que portan ambos temas.

  9. Lipoprotein lipase gene polymorphisms and risks of childhood obesity in Chinese preschool children.

    Science.gov (United States)

    Wang, Li N; Yu, Qing; Xiong, Yan; Liu, Lin F; Zhang, Zhen; Zhang, Xue N; Cheng, Hao; Wang, Bei

    2011-10-01

    Childhood obesity is increasingly prevalent in the community and is related to many adult diseases. Lipoprotein lipase (LPL) plays a central role in dyslipidemia, and polymorphisms of the LPL gene may result in the disturbance in the lipid's metabolism. The aim of this study is to test the hypothesis that genetic variants of LPL and serum lipid levels are associated with the risk of childhood obesity. We genotyped +495T > G and PvuII T > C in an LPL gene and measured the serum lipid levels in a case-control study of 124 obese children and 346 frequency-matched normal controls in preschool Chinese children. The variant genotypes of LPL + 495GG and PvuII CC were associated with a significantly increased risk of childhood obesity [adjusted odds ratio (OR) = 2.39, 95% CI = 1.09-5.23 for +495 GG; adjusted OR = 2.00, 95% CI = 1.04-3.83 for PvuII CC], compared with their wild-type genotypes, respectively. In addition, compared with the lower serum level cut off by the control median, the higher level of serum triglyceride (TG) (>0.59 mmol/L) was associated with a 1.32-fold increased risk of childhood obesity, and the higher level of high density lipoprotein cholesterol (HDLC) (>1.14 mmol/L) was associated with a 36% decrease in risk of childhood obesity. Furthermore, the median levels of TG were higher in obese children carrying LPL +495TT/TG and PvuII TT/CT genotypes than those in controls, the HDLC levels were lower in obese children carrying LPL +495TG and PvuII CT/CC genotypes than those in controls. In conclusion, the LPL gene +495T > G and PvuII T > C polymorphisms may modulate the magnitude of dyslipidemia in Chinese early-onset obesity.

  10. ApoB100/LDLR-/- hypercholesterolaemic mice as a model for mild cognitive impairment and neuronal damage.

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    Carlos Ramírez

    Full Text Available Recent clinical findings support the notion that the progressive deterioration of cholesterol homeostasis is a central player in Alzheimer's disease (AD. Epidemiological studies suggest that high midlife plasma total cholesterol levels are associated with an increased risk of AD. This paper reports the plasma cholesterol concentrations, cognitive performance, locomotor activity and neuropathological signs in a murine model (transgenic mice expressing apoB100 but knockout for the LDL receptor [LDLR] of human familial hypercholesterolaemia (FH. From birth, these animals have markedly elevated LDL-cholesterol and apolipoprotein B100 (apoB100 levels. These transgenic mice were confirmed to have higher plasma cholesterol concentrations than wild-type mice, an effect potentiated by aging. Further, 3-month-old transgenic mice showed cholesterol (total and fractions concentrations considerably higher than those of 18-month-old wild-type mice. The hypercholesterolaemia of the transgenic mice was associated with a clear locomotor deficit (as determined by rotarod, grip strength and open field testing and impairment of the episodic-like memory (determined by the integrated memory test. This decline in locomotor activity and cognitive status was associated with neuritic dystrophy and/or the disorganization of the neuronal microtubule network, plus an increase in astrogliosis and lipid peroxidation in the brain regions associated with AD, such as the motor and lateral entorhinal cortex, the amygdaloid basal nucleus, and the hippocampus. Aortic atherosclerotic lesions were positively correlated with age, although potentiated by the transgenic genotype, while cerebral β-amyloidosis was positively correlated with genetic background rather than with age. These findings confirm hypercholesterolaemia as a key biomarker for monitoring mild cognitive impairment, and shows these transgenic mice can be used as a model for cognitive and psycho-motor decline.

  11. The expression of apoB mRNA editing factors is not the sole determinant for the induction of editing in differentiating Caco-2 cells

    Energy Technology Data Exchange (ETDEWEB)

    Galloway, Chad A. [Department of Biochemistry and Biophysics, University of Rochester School of Medicine, 601 Elmwood Ave., Rochester, NY 14642 (United States); Smith, Harold C., E-mail: harold.smith@rochester.edu [Department of Biochemistry and Biophysics, University of Rochester School of Medicine, 601 Elmwood Ave., Rochester, NY 14642 (United States)

    2010-01-01

    Apolipoprotein B mRNA is edited at cytidine 6666 in the enterocytes lining the small intestine of all mammals; converting a CAA codon to a UAA stop codon. The conversion is {approx}80% efficient in this tissue and leads to the expression of the truncated protein, ApoB48, essential for secretion of dietary lipid as chylomicrons. Caco-2 cell raft cultures have been used as an in vitro model for the induction of editing activity during human small intestinal cell differentiation. This induction of apoB mRNA editing has been ascribed to the expression of APOBEC-1. In agreement our data demonstrated differentiation-dependent induction of expression of the editing enzyme APOBEC-1 and in addition we show alternative splicing of the essential auxiliary factor ACF. However, transfection of these editing factors in undifferentiated proliferating Caco-2 cells was not sufficient to induce robust apoB mRNA editing activity. Only differentiation of Caco-2 cells could induce more physiological like levels of apoB mRNA editing. The data suggested that additional regulatory mechanism(s) were induced by differentiation that controlled the functional activity of editing factors.

  12. Linkage and association analyses identify a candidate region for apoB level on chromosome 4q32.3 in FCHL families.

    Science.gov (United States)

    Wijsman, Ellen M; Rothstein, Joseph H; Igo, Robert P; Brunzell, John D; Motulsky, Arno G; Jarvik, Gail P

    2010-06-01

    Familial combined hyperlipidemia (FCHL) is a complex trait leading to cardiovascular disease (CVD) risk. Elevated levels and size of apolipoprotein B (apoB) and low-density lipoprotein (LDL) are associated with FCHL, which is genetically heterogeneous and is likely caused by rare variants. We carried out a linkage-based genome scan of four large FCHL pedigrees for apoB level that is independent of LDL: apoB level that is adjusted for LDL level and size. Follow-up included SNP genotyping in the region with the strongest evidence of linkage. Several regions with the evidence of linkage in individual pedigrees support the rare variant model. Evidence of linkage was strongest on chromosome 4q, with multipoint analysis in one pedigree giving LOD = 3.1 with a parametric model, and a log Bayes Factor = 1.5 from a Bayesian oligogenic approach. Of the 293 SNPs spanning the implicated region on 4q, rs6829588 completely explained the evidence of linkage. This SNP accounted for 39% of the apoB phenotypic variance, with heterozygotes for this SNP having a trait value that was approximately 30% higher than that of the high-frequency homozygote, thus identifying and considerably refining a strong candidate region. These results illustrate the advantage of using large pedigrees in the search for rare variants: reduced genetic heterogeneity within single pedigrees coupled with the large number of individuals segregating otherwise-rare single variants leads to high power to implicate such variants.

  13. Cinnamon extract attenuates TNF-alpha-induced intestinal lipoprotein ApoB48 overproduction by regulating inflammatory, insulin, and lipoprotein pathways in enterocytes

    Science.gov (United States)

    We evaluated whether a water extract of cinnamon (CE = Cinnulin PF®) attenuates the dyslipidemia induced by TNF-alpha in Triton WR-1339-treated hamsters, and whether CE inhibited the over-secretion of apoB48-induced by TNF-alpha in enterocytes in a 35S-labelling study. In vivo, oral treatment with C...

  14. [Polymorphisms of lipoprotein lipase gene and their participation in metabolic processes].

    Science.gov (United States)

    Barg, Ewa

    2011-01-01

    Lipoprotein lipase (LPL) plays a central role in dyslipidemia and development of metabolic syndrome. The occurrence of polymorphisms of the LPL gene may result in the disturbance in the lipid metabolism and pathogenesis of CAD. Carriers of X447 allele were reported to have lower triglyceride and higher high-density lipoprotein cholesterol levels as well as a reduced risk of CAD. The patiens with hypertriglicerydemia are carriers of common PLP mutations as Asp9Asn,Asn291Ser, Trp86Arg, Gly188Glu, Pro207Leu, and Asp250Asn. LPL is an interesting enzyme that contributes in a pronounced way to normal metabolism, including insulin action, body weight regulation, energy balance, and atherosclerosis. In this rewiev, the roles of polymorphism LPL and their implications in the control of lipoprotein metabolism and atherosclerosis are discussed, especially in the group of risk developing metabolic syndrome - children with low birth weight (below 2500 g).

  15. Induction of body weight loss through RNAi-knockdown of APOBEC1 gene expression in transgenic rabbits.

    Directory of Open Access Journals (Sweden)

    Geneviève Jolivet

    Full Text Available In the search of new strategies to fight against obesity, we targeted a gene pathway involved in energy uptake. We have thus investigated the APOB mRNA editing protein (APOBEC1 gene pathway that is involved in fat absorption in the intestine. The APOB gene encodes two proteins, APOB100 and APOB48, via the editing of a single nucleotide in the APOB mRNA by the APOBEC1 enzyme. The APOB48 protein is mandatory for the synthesis of chylomicrons by intestinal cells to transport dietary lipids and cholesterol. We produced transgenic rabbits expressing permanently and ubiquitously a small hairpin RNA targeting the rabbit APOBEC1 mRNA. These rabbits exhibited a moderately but significantly reduced level of APOBEC1 gene expression in the intestine, a reduced level of editing of the APOB mRNA, a reduced level of synthesis of chylomicrons after a food challenge, a reduced total mass of body lipids and finally presented a sustained lean phenotype without any obvious physiological disorder. Interestingly, no compensatory mechanism opposed to the phenotype. These lean transgenic rabbits were crossed with transgenic rabbits expressing in the intestine the human APOBEC1 gene. Double transgenic animals did not present any lean phenotype, thus proving that the intestinal expression of the human APOBEC1 transgene was able to counterbalance the reduction of the rabbit APOBEC1 gene expression. Thus, a moderate reduction of the APOBEC1 dependent editing induces a lean phenotype at least in the rabbit species. This suggests that the APOBEC1 gene might be a novel target for obesity treatment.

  16. Relación entre tipo y cantidad de carbohidratos dietarios con el perfil lipídico y ApoB100 en adultos

    OpenAIRE

    Ojeda-Arredondo, Myriam; Departamento de Nutrición y Bioquímica. Facultad de Ciencias. Pontificia Universidad Javeriana, Bogotá, D.C.; Escobar, Juliana; Departamento de Nutrición y Bioquímica. Facultad de Ciencias. Pontificia Universidad Javeriana, Bogotá, D.C.; Guerra, Martha; Departamento de Nutrición y Bioquímica. Facultad de Ciencias. Pontificia Universidad Javeriana, Bogotá, D.C.; Alvarado, Martha; Departamento de Nutrición y Bioquímica. Facultad de Ciencias. Pontificia Universidad Javeriana, Bogotá, D.C.

    2010-01-01

    Objetivo. Establecer si existe relación entre el tipo y la cantidad de carbohidratos dietarios consumidos habitualmente con los niveles plasmáticos de lípidos, lipoproteínas y apolipoproteína B100 (ApoB100) Materiales y métodos. La muestra estuvo conformada por la base de datos de 144 de profesores de la Universidad Javeriana que previamente hicieron parte de otra investigación y de la cual se empleo la información sobre su alimentación, niveles plasmáticos de lípidos, lipoproteínas y ApoB100...

  17. Subjects with molecularly defined familial hypercholesterolemia or familial defective apoB-100 are not being adequately treated.

    Directory of Open Access Journals (Sweden)

    Trond P Leren

    Full Text Available OBJECTIVES: To study whether subjects with a molecular genetic diagnosis of familial hypercholesterolemia (FH or familial defective apoB-100 (FDB are being adequately treated. DESIGN: A questionnaire regarding medical history was sent to 2611 subjects who had been provided with a molecular genetic diagnosis of FH or FDB, and a blood sample was obtained for lipid measurements. RESULTS: 956 (36.6% of the 2611 subjects participated. The mean age for starting lipid-lowering therapy was 33.4 (±12.1 years. Among those below 18 years of age, only 20.4% were on lipid-lowering drugs, whereas 89.1% of those aged 18 and above were on lipid-lowering drugs. The mean levels of total serum cholesterol and LDL-cholesterol were 5.7 (±1.5 mmol/l and 3.9 (±1.3 mmol/l, respectively. Among those who were on lipid-lowering drugs, 29.0% and 12.2% had levels of LDL cholesterol below 3.0 mmol/l and 2.6 mmol/l, respectively. Only 47.3% of the 956 subjects were considered as being adequately treated largely due to a failure to titrate their drug regimens. From the use of cholesterol-years score, lipid-lowering therapy must start before the age of 20 in order to prevent the subjects from contracting premature coronary heart disease. CONCLUSION: The majority of FH/FDB subjects are being diagnosed late in life and are not being adequately treated. In order to prevent them from contracting premature coronary heart disease, it is key that levels of LDL cholesterol are normalized from a young age and that sufficient doses of lipid-lowering drugs are being used.

  18. [The relation between gene of lipoprotein-lipase and carrier protein of cholesterol ethers and life duration in patients with chronic cerebral ischemia].

    Science.gov (United States)

    Kostomarov, I V; Vodolagina, N N; Malygina, N A; Mitina, Z S

    2008-01-01

    Comparative analysis of frequency distribution of genotypes and alleles of HindIII-polymorphism of gene LPL and TaqIB-polymorphism of gene CETP in 267 patients of various ages with chronic cerebral ischemia (CCI) was performed. Relation between age and polymorphous variants of genes LPL and CETP was noticed. It was shown that genotype of H+H+ HindIII-polymorphism of and genotype B1B1 TaqIB-polymorphism of gene CETP were found more frequently in more young patients with chronic cerebral ischemia (CCI). Since there is an association of these genotypes with atherogenic dislipidemias, they apparently can be considered as risk factors of CCI development. On the contrary, genotype of gene LPL and B2 allele of gene CETP in patients elder 90 years (long-livers) are found significantly more frequently than in younger patients, that makes possible to consider they as markers of favorable course of disease and patients' long life.

  19. Lipoprotein lipase gene variants: Association with acute myocardial ...

    African Journals Online (AJOL)

    Mahyar Bahrami

    2015-05-13

    May 13, 2015 ... morphism (rs320) is located in position 495 of LPL gene's intron 8th. In this ... a control group, 203 age-matched individuals with normal coronary .... motifs for Ascl2 and NHLH1 transcription factor binding sites. (Fig 1) [29].

  20. Generation and characterization of two novel mouse models exhibiting the phenotypes of the metabolic syndrome: Apob48-/-Lepob/ob mice devoid of ApoE or Ldlr.

    Science.gov (United States)

    Lloyd, David J; McCormick, Jocelyn; Helmering, Joan; Kim, Ki Won; Wang, Minghan; Fordstrom, Preston; Kaufman, Stephen A; Lindberg, Richard A; Véniant, Murielle M

    2008-03-01

    The metabolic syndrome is a group of disorders including obesity, insulin resistance, atherogenic dyslipidemia, hyperglycemia, and hypertension. To date, few animal models have been described to recapitulate the phenotypes of the syndrome. In this study, we generated and characterized two lines of triple-knockout mice that are deficient in either apolipoprotein E (Apoe(-/-)) or low-density lipoprotein receptor (Ldlr(-/-)) and express no leptin (Lep(ob/ob)) or apolipoprotein B-48 but exclusively apolipoprotein B-100 (Apob(100/100)). These two lines are referred to as Apoe triple-knockout-Apoe 3KO (Apoe(-/-)Apob(100/100)Lep(ob/ob)) and Ldlr triple-knockout-Ldlr 3KO (Ldlr(-/-)Apob(100/100)Lep(ob/ob)) mice. Both lines develop obesity, hyperinsulinemia, hyperlipidemia, hypertension, and atherosclerosis. However, only Apoe 3KO mice are hyperglycemic and glucose intolerant and are more obese than Ldlr 3KO mice. To evaluate the utility of these lines as pharmacological models, we treated both with leptin and found that leptin therapy ameliorated most metabolic derangements. Leptin was more effective in improving glucose tolerance in Ldlr 3KO than Apoe 3KO animals. The reduction of plasma cholesterol by leptin in Ldlr 3KO mice can be accounted for by its suppressive effect on food intake. However, in Apoe 3KO mice, leptin further reduced plasma cholesterol independently of its effect on food intake, and this improvement correlated with a smaller plaque lesion area. These effects suggest a direct role of leptin in modulating VLDL levels and, likewise, the lesion areas in VLDL-enriched animals. These two lines of mice represent new models with features of the metabolic syndrome and will be useful in testing therapies targeted for combating the human condition.

  1. Leu452His mutation in lipoprotein lipase gene transfer associated with hypertriglyceridemia in mice in vivo.

    Directory of Open Access Journals (Sweden)

    Kaiyue Sun

    Full Text Available Mutated mouse lipoprotein lipase (LPL containing a leucine (L to histidine (H substitution at position 452 was transferred into mouse liver by hydrodynamics-based gene delivery (HD. Mutated-LPL (MLPL gene transfer significantly increased the concentrations of plasma MLPL and triglyceride (TG but significantly decreased the activity of plasma LPL. Moreover, the gene transfer caused adiposis hepatica and significantly increased TG content in mouse liver. To understand the effects of MLPL gene transfer on energy metabolism, we investigated the expression of key functional genes related to energy metabolism in the liver, epididymal fat, and leg muscles. The mRNA contents of hormone-sensitive lipase (HSL, adipose triglyceride lipase (ATGL, fatty acid-binding protein (FABP, and uncoupling protein (UCP were found to be significantly reduced. Furthermore, we investigated the mechanism by which MLPL gene transfer affected fat deposition in the liver, fat tissue, and muscle. The gene expression and protein levels of forkhead Box O3 (FOXO3, AMP-activated protein kinase (AMPK, and peroxisome proliferator-activated receptor-gamma coactivator 1 alpha (PGC-1α were found to be remarkably decreased in the liver, fat and muscle. These results suggest that the Leu452His mutation caused LPL dysfunction and gene transfer of MLPL in vivo produced resistance to the AMPK/PGC-1α signaling pathway in mice.

  2. Association of structural variants of the gene of apolipoprotein B with coronary heart disease and serum lipid level

    Energy Technology Data Exchange (ETDEWEB)

    Stepanov, V.A.; Puzyrev, V.P.; Lemza, S.V. [Institute of Medical Genetics, Tomsk (Russian Federation); Karpov, R.S.; Fedorov, A.Yu. [Institute of Cardiology, Tomsk (Russian Federation)

    1995-07-01

    Xba I and EcoR I polymorphism of the apolipoprotein B (APOB) gene was studied by PCR. A significant increase in the frequency of allele X{sup +} and haplotype X{sup +}E{sup +} was demonstrated in patients with coronarographically documented coronary heart disease (CHD) over that of the general population. Association of allele E{sup {minus}} with increased levels of serum triglycerides was found. The results provide evidence about the contribution of structural variants of the APOB gene to determining CHD. 21 refs., 4 tabs.

  3. The elevation of apoB in hypercholesterolemic patients is primarily attributed to the relative increase of apoB/Lp-PLA₂.

    Science.gov (United States)

    Tellis, Constantinos C; Moutzouri, Eliza; Elisaf, Moses; Wolfert, Robert L; Tselepis, Alexandros D

    2013-12-01

    Lipoprotein-associated phospholipase A₂ (Lp-PLA₂) is a risk factor of cardiovascular disease. Plasma Lp-PLA₂ is mainly associated with apolipoprotein (apo)B-containing lipoproteins, primarily with low density lipoproteins (LDLs). Importantly, only a proportion of circulating lipoproteins contain Lp-PLA₂. We determined the plasma levels of Lp-PLA₂-bound apoB (apoB/Lp-PLA₂) in patients with primary hypercholesterolemia. The effect of simvastatin therapy was also addressed. The plasma apoB/Lp-PLA₂ concentration in 50 normolipidemic controls and 53 patients with primary hypercholesterolemia at baseline and at 3 months posttreatment with simvastatin (40 mg/day) was determined by an enzyme-linked immunosorbent assay. The concentration of the apoB-containing lipoproteins that do not bind Lp-PLA₂ [apoB/Lp-PLA₂⁻] was calculated by subtracting the apoB/Lp-PLA₂ from total apoB. The apoB/Lp-PLA₂ levels were 3.6-fold higher, while apoB/Lp-PLA₂⁻ were 1.3-fold higher in patients compared with controls. After 3 months of simvastatin treatment apoB/Lp-PLA₂ and apoB/Lp-PLA₂⁻ levels were reduced by 52% and 33%, respectively. The elevation in apoB-containing lipoproteins in hypercholesterolemic patients is mainly attributed to the relative increase in the proatherogenic apoB/Lp-PLA₂, while simvastatin reduces these particles to a higher extent compared with apoB/Lp-PLA₂⁻. Considering that Lp-PLA₂ is proatherogenic, the predominance of apoB/Lp-PLA₂ particles in hypercholesterolemic patients may contribute to their higher atherogenicity and incidence of cardiovascular disease.

  4. Acidity and lipolysis by group V secreted phospholipase A(2) strongly increase the binding of apoB-100-containing lipoproteins to human aortic proteoglycans.

    Science.gov (United States)

    Lähdesmäki, Katariina; Öörni, Katariina; Alanne-Kinnunen, Mervi; Jauhiainen, Matti; Hurt-Camejo, Eva; Kovanen, Petri T

    2012-02-01

    Local acidic areas characterize diffuse intimal thickening (DIT) and advanced atherosclerotic lesions. The role of acidity in the modification and extra- and intracellular accumulation of triglyceride-rich VLDL and IDL particles has not been studied before. Here, we examined the effects of acidic pH on the activity of recombinant human group V secreted phospholipase A(2) (sPLA(2)-V) toward small VLDL (sVLDL), IDL, and LDL, on the binding of these apoB-100-containing lipoproteins to human aortic proteoglycans, and on their uptake by human monocyte-derived macrophages. At acidic pH, the ability of sPLA(2)-V to lipolyze the apoB-100-containing lipoproteins was moderately, but significantly, increased while binding of the lipoproteins to proteoglycans increased >60-fold and sPLA(2)-V-modification further doubled the binding. Moreover, acidic pH more than doubled macrophage uptake of soluble complexes of sPLA(2)-V-LDL with aortic proteoglycans. Proteoglycan-affinity chromatography at pH 7.5 and 5.5 revealed that sVLDL, IDL, and LDL consisted of populations with different proteoglycan-binding affinities, and, surprisingly, the sVLDL fractions with the highest proteoglycan-affinity contained only low amounts of apolipoproteins E and C-III. Our results suggest that in atherosclerotic lesions with acidic extracellular pH, sPLA(2)-V is able to lipolyze sVLDL, IDL, and LDL, and increase their binding to proteoglycans. This is likely to provoke extracellular accumulation of lipids derived from these atherogenic lipoprotein particles and to increase the progression of the atherosclerotic lesions.

  5. Impact of lipoprotein lipase gene polymorphisms on ulcerative colitis

    Institute of Scientific and Technical Information of China (English)

    Toshihito Kosaka; Taizou Shiraishi; Masatoshi Watanabe; Takayuki Yamamoto; Ai Nakahara; Takahiko Katoh; Junji Yoshino; Kazuo Inui; Takao Wakabayashi; Kazumu Okushima; Takashi Kobayashi; Hironao Miyoshi; Yuta Nakamura; Shigekazu Hayashi

    2006-01-01

    AIM: To examine the influence of lipoprotein lipase (LPL)gene polymorphism in ulcerative colitis (UC) patients.METHODS: Peripheral blood was obtained from 131 patients with UC and 106 healthy controls for DNA extraction. We determined LPL gene polymorphisms affecting the enzyme at Ser447stop, as well as Hind Ⅲ and Pvu Ⅱ polymorphisms using PCR techniques. PCR products were characterized by PCR-RFLP and direct sequencing.Polymorphisms were examined for association with clinical features in UC patients. Genotype frequencies for LPL polymorphisms were also compared between UC patients and controls.RESULTS: In patients with onset at age 20 years or younger, C/G and G/G genotypes for Ser447stop polymorphism were more prevalent than C/C genotype (OR= 3.13, 95% CI = 0.95-10.33). Patients with H+/- or H-/-genotype for HindⅢ polymorphism also were more numerous than those with H+/+ genotype (OR = 2.51, 95%CI = 0.85-7.45). In the group with H+/+ genotype for HindⅢ polymorphism, more patients had serum triglyceride concentrations over 150 mg/dL than patients with H+/- or H-/- genotype (P < 0.01, OR = 6.46, 95% CI =1.39-30.12). Hypertriglycemia was also more prevalent in patients with P+/+ genotypes for Pvu Ⅱ polymorphism (P< 0.05, OR = 3.0, 95% CI = 1.06-8.50). Genotype frequency for LPL polymorphism did not differ significantly between UC patients and controls.CONCLUSION: Ser447stop and HindⅢ LPL polymorphisms may influence age of onset of UC, while HindⅢand PvuⅡ polymorphisms influence serum triglyceride in UC patients.

  6. Relationship between a lipoprotein lipase gene polymorphism in placental tissue and insulin resistance in patients with gestational diabetes mellitus.

    Science.gov (United States)

    Li, D D; Su, D Y; Xue, L; Gao, W; Pang, W Y

    2015-07-14

    The aim of this study was to investigate the relationship between a lipoprotein lipase (LPL) gene polymorphism in placental tissue and insulin resistance (IR) in patients with gestational diabetes mellitus. Using polymerase chain reaction-restriction enzyme fragment length polymorphism (PCR-RFLP) analysis, the LPL HindIII RFLP was examined in the placental tissue of 110 patients with gestational diabetes mellitus (observation group) and 110 women with normal gestation (control group). The relationships between fasting plasma glucose (FPG), postprandial plasma glucose (PPG), fasting insulin (FINS), cholesterol (TC), triglyceride (TG), high density lipoprotein (HDL), low density lipoprotein (LDL), body mass index (BMI), and IR indices and the LPL polymorphism in the two study groups and their offspring were determined. The frequency of the H+ allele was significantly higher in the observation group than in the controls (P diabetes, and was also found to be related to the IR of their offspring.

  7. Severe hypertriglyceridemia in a patient heterozygous for a lipoprotein lipase gene allele with two novel missense variants.

    Science.gov (United States)

    Kassner, Ursula; Salewsky, Bastian; Wühle-Demuth, Marion; Szijarto, Istvan Andras; Grenkowitz, Thomas; Binner, Priska; März, Winfried; Steinhagen-Thiessen, Elisabeth; Demuth, Ilja

    2015-09-01

    Rare monogenic hyperchylomicronemia is caused by loss-of-function mutations in genes involved in the catabolism of triglyceride-rich lipoproteins, including the lipoprotein lipase gene, LPL. Clinical hallmarks of this condition are eruptive xanthomas, recurrent pancreatitis and abdominal pain. Patients with LPL deficiency and severe or recurrent pancreatitis are eligible for the first gene therapy treatment approved by the European Union. Therefore the precise molecular diagnosis of familial hyperchylomicronemia may affect treatment decisions. We present a 57-year-old male patient with excessive hypertriglyceridemia despite intensive lipid-lowering therapy. Abdominal sonography showed signs of chronic pancreatitis. Direct DNA sequencing and cloning revealed two novel missense variants, c.1302A>T and c.1306G>A, in exon 8 of the LPL gene coexisting on the same allele. The variants result in the amino-acid exchanges p.(Lys434Asn) and p.(Gly436Arg). They are located in the carboxy-terminal domain of lipoprotein lipase that interacts with the glycosylphosphatidylinositol-anchored HDL-binding protein (GPIHBP1) and are likely of functional relevance. No further relevant mutations were found by direct sequencing of the genes for APOA5, APOC2, LMF1 and GPIHBP1. We conclude that heterozygosity for damaging mutations of LPL may be sufficient to produce severe hypertriglyceridemia and that chylomicronemia may be transmitted in a dominant manner, at least in some families.

  8. Haplotypes in the lipoprotein lipase gene influence fasting insulin and discovery of a new risk haplotype.

    Science.gov (United States)

    Goodarzi, Mark O; Taylor, Kent D; Guo, Xiuqing; Hokanson, John E; Haffner, Steven M; Cui, Jinrui; Chen, Yii-Der I; Wagenknecht, Lynne E; Bergman, Richard N; Rotter, Jerome I

    2007-01-01

    Prior studies of Mexican Americans described association of lipoprotein lipase (LPL) gene haplotypes with insulin sensitivity/resistance and atherosclerosis. The most common haplotype (haplotype 1) was protective, whereas the fourth most common haplotype (haplotype 4) conferred risk for insulin resistance and atherosclerosis. In this study of Hispanics in the Insulin Resistance Atherosclerosis Study Family Study, we sought to replicate LPL haplotype association with insulin sensitivity/resistance. LPL haplotypes based on 12 single nucleotide polymorphisms were analyzed for association with indexes of insulin sensitivity and other metabolic and adiposity measures. This study was conducted in the general community of San Antonio, Texas, and San Luis Valley, Colorado. Participants in this study were 978 members of 86 Hispanic families. LPL haplogenotype, metabolic phenotypes, and adiposity were measured in this study. The haplotype structure was identical with that observed in prior studies. Among 978 phenotyped subjects, haplotype 1 was associated with decreased fasting insulin (P = 0.01), and haplotype 4 was associated with increased fasting insulin (P = 0.02) and increased visceral fat mass (P = 0.002). Insulin sensitivity, derived from iv glucose tolerance testing, tended (P > 0.1) to be higher with haplotype 1 (S(I) = 1.72) and lower with haplotype 4 (S(I)=1.38). Haplotype 2 was associated with increases in fasting insulin, triglycerides (TGs), TG to high-density lipoprotein-cholesterol ratio, and apolipoprotein B (P = 0.01-0.04). This study independently replicates our prior results of LPL haplotypes 1 and 4 as associated with measures of insulin sensitivity and resistance, respectively. Haplotype 4 may confer insulin resistance by increasing visceral fat. Haplotype 2 was identified as a new risk haplotype, suggesting the complex nature of LPL's effect on features of the insulin resistance syndrome.

  9. Physiological Study of Lipoprotein Lipase Gene Pvu II Polymorphism in Cases of Obesity in Egypt

    Directory of Open Access Journals (Sweden)

    Ghada El-Kannishy

    2012-01-01

    Full Text Available Genetic predisposition has been implicated in obesity. Lipoprotein lipase (LPL gene, the main lipase of chylomicrons and Low Density Lipoproteins (LDL, has a fundamental role in the transport and metabolism of plasma cholesterol. The present study was undertaken to test for the association of the LPL gene Pvu II polymorphism with obesity with or without hypertension and diabetes and dyslipidemia among affected Egyptian cases. This study has included 120 subjects affected with obesity; 57 of them were affected with metabolic syndrome (with diabetes, dyslipidemia and hypertension while the other 63 cases were not complicated and were termed simple obesity. These cases were compared to 83 healthy non-obese controls. Body Mass Index (BMI, Waist Hip Ration (WHR and serum lipid levels were measured. The LPL gene polymorphic alleles were determined by PCR-RFLP that includes polymerase chain reaction for gene amplification followed by digestion with Pvu II enzyme and analysis according to the size of digested amplified DNA. Obesity cases had a significantly higher frequency of the homozygous mutated LPL Pvu II (+/+ genotype and also of the (+ allele particularly among metabolic syndrome cases compared to controls. Cases with the (+/+ homozygous genotype showed significantly higher frequency of diabetes, lower frequency of positive family history and lower values for waist hip ratio than those with the (+/- and (-/- genotypes. These cases have showed also higher levels of total cholesterol and LDL-C, yet not reaching statistical significance. This study showed a significant association between the LPL Pvu II gene polymorphism and obesity among Egyptian cases particularly when complicated with the metabolic syndrome.

  10. Key intestinal genes involved in lipoprotein metabolism are downregulated in dyslipidemic men with insulin resistance.

    Science.gov (United States)

    Couture, Patrick; Tremblay, André J; Kelly, Isabelle; Lemelin, Valéry; Droit, Arnaud; Lamarche, Benoît

    2014-01-01

    Insulin resistance (IR) is associated with elevated plasma levels of triglyceride-rich lipoproteins (TRLs) of intestinal origin. However, the mechanisms underlying the overaccumulation of apolipoprotein (apo)B-48-containing TRLs in individuals with IR are not yet fully understood. This study examined the relationships between apoB-48-containing TRL kinetics and the expression of key intestinal genes and proteins involved in lipid/lipoprotein metabolism in 14 obese nondiabetic men with IR compared with 10 insulin-sensitive (IS) men matched for waist circumference. The in vivo kinetics of TRL apoB-48 were assessed using a primed-constant infusion of L-[5,5,5-D₃]leucine for 12 h with the participants in a constantly fed state. The expression of key intestinal genes and proteins involved in lipid/lipoprotein metabolism was assessed by performing real-time PCR quantification and LC-MS/MS on duodenal biopsy specimens. The TRL apoB-48 pool size and production rate were 102% (P < 0.0001) and 87% (P = 0.01) greater, respectively, in the men with IR versus the IS men. On the other hand, intestinal mRNA levels of sterol regulatory element binding factor-2, hepatocyte nuclear factor-4α, and microsomal triglyceride transfer protein were significantly lower in the men with IR than in the IS men. These data indicate that IR is associated with intestinal overproduction of lipoproteins and significant downregulation of key intestinal genes involved in lipid/lipoprotein metabolism.

  11. 脂蛋白脂酶缺失症基因治疗载体的构建及功能验证%Construction and Verification of Gene Therapy Vector for Lipoprotein Lipase Deficiency Disease

    Institute of Scientific and Technical Information of China (English)

    王恺龙; 郑李彬; 张帆; 沈良才; Libby Andrew; 李旭丽; 张瑾

    2013-01-01

    脂蛋白脂酶(lipoprotein lipase,LPL)是甘油三酯分解的限速酶,LPL基因缺失会引起高血脂症,虽然发病率低,但到目前为止,尚无有效治疗手段.该文构建了用于纠正LPL缺失基因型的逆转录病毒载体MSCV-hLPL,结果表明,MSCV-hLPL可以高效侵染体外培养的细胞系C2C12、HEK293和3T3-L1,并且都可以产生具有活性的脂蛋白脂酶.利用MSCV-hLPL侵染后的C2C12、HEK293和3T3-L1,分别注射到裸鼠皮下组织,发现C2C12和3T3-L1可以分泌脂蛋白脂酶到临近的肌肉组织中,显著提高LPL活性.以上工作证明,基因治疗载体可以纠正脂蛋白脂酶缺失的基因型,而脂肪细胞和肌肉细胞移植入裸鼠体内后,均可以作为生物反应器产生具有活性的LPL.这是该领域中的一次开拓性尝试,为脂蛋白脂酶缺失症治疗方法的开发打下了坚实的基础.%Lipoprotein lipase (LPL) is the rate limiting enzyme for triglycerides hydrolysis,which catalyses the hydrolysis of the triacylglycerol component of chylomicrons and very low density lipoproteins,thereby providing fatty acids and monoacylglycerol for tissue utilization.LPL gene mutation or deletion may affect the activity of LPL,and result in lipid metabolism disorder.Although the LPL deficiency disease is rare,no cure method is developed till now.In this study,the gene therapy construct MSCV-hLPL was made,which could infect muscle cell line (C2C12),kidney cell line (HEK293T) and pre-adipocyte cell line (3T3-L1) with over 80% efficiency.Nevertheless,active LPL could be detected at the surface of all these three kinds of cells.Then,three types of cells were injected into nude mice,LPL activity increased significantly in the muscle tissues under the injection sites of the 3T3-L1 line.Our results show that MSCV-hLPL could correct the LPL-/-genotype and the adipose tissue may be the best tissue for transplantation in the future.This is a ground-breaking test in LPL deficiency treatment field

  12. SINGLE NUCLEOTIDE POLYMORPHISMS OF LIPOPROTEIN LIPASE GENE AND ITS ASSOCIATION WITH MARBLING QUALITY IN LOCAL SHEEPS

    Directory of Open Access Journals (Sweden)

    H. Hidayati

    2015-09-01

    Full Text Available Lipoprotein lipase (LPL is a key enzyme that plays in metabolism and transport lipoprotein andtherefore has an influence on blood triglyceride levels. LPL controls triacylglycerol partitioning betweenadipose tissue and muscle that increases fat storage or provides energy in the form of fatty acids formuscle growth. The research was aimed to explore Single Nucleotide Polymorphisms of LPL gene andto associate SNP with marbling quality. A total of 66 genomic DNAs consisted of sumatera thin-tail edsheep (50 heads and garut sheep (16 heads were used in this study. Polymerase Chain Reaction wasused to amplify genomic DNA and direct sequencing method was to identify polymorphism sequences.The sequences were analyzed with Bio Edit and MEGA 5.2. The BLAST sequence was obtained fromgene bank X.68308.1. The association between the genotype and marbling quality was analyze by oneway ANOVA and further between mean differences were tested using least sgnificant difference. Theresults showed that 3 novel SNPs i.e. insertion g.26>C; insertion g.27> G and c.192T>C on garut sheepand a SNP insertion g.26>C/G on sumatera thin-tail ed sheep. The diversity of LPL gene at c.192T>Cwas associated with heneicosanoic acid, whereas TT genotype (0.04% was higher than CC (0.03% andCT (0.02%.

  13. Echium Oil Reduces Plasma Triglycerides by Increasing Intravascular Lipolysis in apoB100-Only Low Density Lipoprotein (LDL Receptor Knockout Mice

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    John S. Parks

    2013-07-01

    Full Text Available Echium oil (EO, which is enriched in SDA (18:4 n-3, reduces plasma triglyceride (TG concentrations in humans and mice. We compared mechanisms by which EO and fish oil (FO reduce plasma TG concentrations in mildly hypertriglyceridemic male apoB100-only LDLrKO mice. Mice were fed one of three atherogenic diets containing 0.2% cholesterol and palm oil (PO; 20%, EO (10% EO + 10% PO, or FO (10% FO + 10% PO. Livers from PO- and EO-fed mice had similar TG and cholesteryl ester (CE content, which was significantly higher than in FO-fed mice. Plasma TG secretion was reduced in FO vs. EO-fed mice. Plasma very low density lipoprotein (VLDL particle size was ordered: PO (63 ± 4 nm > EO (55 ± 3 nm > FO (40 ± 2 nm. Post-heparin lipolytic activity was similar among groups, but TG hydrolysis by purified lipoprotein lipase was significantly greater for EO and FO VLDL compared to PO VLDL. Removal of VLDL tracer from plasma was marginally faster in EO vs. PO fed mice. Our results suggest that EO reduces plasma TG primarily through increased intravascular lipolysis of TG and VLDL clearance. Finally, EO may substitute for FO to reduce plasma TG concentrations, but not hepatic steatosis in this mouse model.

  14. Echium oil reduces plasma triglycerides by increasing intravascular lipolysis in apoB100-only low density lipoprotein (LDL) receptor knockout mice.

    Science.gov (United States)

    Forrest, Lolita M; Lough, Christopher M; Chung, Soonkyu; Boudyguina, Elena Y; Gebre, Abraham K; Smith, Thomas L; Colvin, Perry L; Parks, John S

    2013-07-12

    Echium oil (EO), which is enriched in SDA (18:4 n-3), reduces plasma triglyceride (TG) concentrations in humans and mice. We compared mechanisms by which EO and fish oil (FO) reduce plasma TG concentrations in mildly hypertriglyceridemic male apoB100-only LDLrKO mice. Mice were fed one of three atherogenic diets containing 0.2% cholesterol and palm oil (PO; 20%), EO (10% EO + 10% PO), or FO (10% FO + 10% PO). Livers from PO- and EO-fed mice had similar TG and cholesteryl ester (CE) content, which was significantly higher than in FO-fed mice. Plasma TG secretion was reduced in FO vs. EO-fed mice. Plasma very low density lipoprotein (VLDL) particle size was ordered: PO (63 ± 4 nm) > EO (55 ± 3 nm) > FO (40 ± 2 nm). Post-heparin lipolytic activity was similar among groups, but TG hydrolysis by purified lipoprotein lipase was significantly greater for EO and FO VLDL compared to PO VLDL. Removal of VLDL tracer from plasma was marginally faster in EO vs. PO fed mice. Our results suggest that EO reduces plasma TG primarily through increased intravascular lipolysis of TG and VLDL clearance. Finally, EO may substitute for FO to reduce plasma TG concentrations, but not hepatic steatosis in this mouse model.

  15. Lipoprotein lipase gene deficiency accelerates early renal dysfunctions in type 1 diabetic mice%脂蛋白脂酶基因缺陷加重小鼠1型糖尿病肾病的早期进展

    Institute of Scientific and Technical Information of China (English)

    周晓琳; 王兆红; 王宇辉; 沈蔷; 张玲; 管又飞; 刘国庆; 黄薇

    2012-01-01

    目的 探讨脂蛋白脂酶(LPL)基因缺陷对小鼠1型糖尿病(T1DM)肾病早期病变的影响.方法 雄性LPL基因缺陷杂合子(LK)和野生型(WT)小鼠腹腔注射链脲佐菌素(STZ),造成T1DM模型后4个月检测相应指标的改变.结果 糖尿病组血糖、血浆TG及TC、肾重/体重比、肌酐清除率(Ccr)、24 h尿白蛋白(UAlb)含量、肾小球表面积均高于非糖尿病组.糖尿病LK组(DLK)与糖尿病WT组(DWT)相比,血浆TG水平、UAlb及血压均增高(P<0.05).与TG合成相关的核转录因子固醇调节元件结合蛋白-1c(SREBP-1c)基因在DLK组比DWT组表达明显增加(P<0.05),但肾TG含量无改变.结论 LPL基因缺陷促进T1DM小鼠UAlb含量及血压升高,加重T1 DM早期的进展.%Objective To investigate the effect of lipoprotein lipase (LPL) gene deficiency on early stage of type 1 diabetic nephropathy (DN) in mice Methods At 4 months after induction of diabetes by STZ, plasma and renal parameters were examined in heterozygous LPL knock out (LKO) and wide-type (WT) mice. Results (l)Compared with control groups, diabetic groups showed the increased levels of creatinine clearance rate, 24-hour urinary albumin excretion (UAE) and glomerular surface area, which suggested it was at the incipient stage of DN. (2 ) Plasma triglyceride ( P< 0. 05), UAE (P< 0. 01) and blood pressure (P<0. 05)increased in diabetic LKO (DLKO) mice than in diabetic WT (DWT) mice. (3) Real time PCR analysis showed that renal LPL mRNA expression was decreased in LPL deficiency group and diabetes group. Expression of sterol regulatory element binding protein-lc was up-regulated in DLKO mice compared with DWT mice (P<0. 05), but renal lipid deposition didn't differ between 2 groups. Conclusions LPL gene deficiency increases albuminuria and blood pressure in type 1 diabetic mice, suggesting LPL gene deficiency may enhance development of early stage of DN in mice.Objective To investigate the effect of lipoprotein lipase (LPL) gene

  16. The expression of type III hyperlipoproteinemia: involvement of lipolysis genes

    Science.gov (United States)

    Henneman, Peter; van der Sman-de Beer, Femke; Moghaddam, Payman Hanifi; Huijts, Petra; Stalenhoef, Anton FH; Kastelein, John JP; van Duijn, Cornelia M; Havekes, Louis M; Frants, Rune R; van Dijk, Ko Willems; Smelt, Augustinus HM

    2009-01-01

    Type III hyperlipoproteinemia (HLP) is mainly found in homozygous apolipoprotein (APO) E2 (R158C) carriers. Genetic factors contributing to the expression of type III HLP were investigated in 113 hyper- and 52 normolipidemic E2/2 subjects, by testing for polymorphisms in APOC3, APOA5, HL (hepatic lipase) and LPL (lipoprotein lipase) genes. In addition, 188 normolipidemic Dutch control panels (NDCP) and 141 hypertriglyceridemic (HTG) patients were genotyped as well. No associations were found for four HL gene polymorphisms and two LPL gene polymorphisms and type III HLP. The frequency of the rare allele of APOC3 3238 G>C and APOA5 −1131 T>C (in linkage disequilibrium) was significantly higher in type III HLP patients when compared with normolipidemic E2/2 subjects, 15.6 vs 6.9% and 15.1 vs 5.8%, respectively, (PC polymorphism and LPL c.27 G>A mutation were higher in type III HLP patients, though not significant. Some 58% of the type III HLP patients carried either the APOA5 −1131 T>C, c.56 G>C and/or LPL c.27 G>A mutation as compared to 27% of the normolipidemic APOE2/2 subjects (odds ratio 3.7, 95% confidence interval=1.8–7.5, PC/APOA5 −1131 T>C polymorphism showed a more severe hyperlipidemia than patients without this polymorphism. Polymorphisms in lipolysis genes associate with the expression and severity of type III HLP in APOE2/2. PMID:19034316

  17. Effects of extended-release niacin on the postprandial metabolism of Lp(a) and ApoB-100-containing lipoproteins in statin-treated men with type 2 diabetes mellitus.

    Science.gov (United States)

    Ooi, Esther M; Watts, Gerald F; Chan, Dick C; Pang, Jing; Tenneti, Vijay S; Hamilton, Sandra J; McCormick, Sally P; Marcovina, Santica M; Barrett, P Hugh R

    2015-12-01

    The effects of extended-release niacin (ERN; 1-2 g/d) on the metabolism of lipoprotein(a) (Lp(a)) and apolipoprotein (apo) B-100-containing lipoproteins were investigated in 11 statin-treated white men with type 2 diabetes mellitus in a randomized, crossover trial of 12-weeks duration. The kinetics of Lp(a) and very low-density lipoprotein (VLDL), intermediate-density lipoprotein, and low-density lipoprotein (LDL) apoB-100 were determined following a standardized oral fat load (87% fat) using intravenous administration of D3-leucine, gas chromatography-mass spectrometry, and compartmental modeling. ERN significantly decreased fasting plasma total cholesterol, LDL cholesterol, and triglyceride concentrations. These effects were achieved without significant changes in body weight or insulin resistance. ERN significantly decreased plasma Lp(a) concentration (-26.5%) and the production rates of apo(a) (-41.5%) and Lp(a)-apoB-100 (-32.1%); the effect was greater in individuals with elevated Lp(a) concentration. ERN significantly decreased VLDL (-58.7%), intermediate-density lipoprotein (-33.6%), and LDL (-18.3%) apoB-100 concentrations and the corresponding production rates (VLDL, -49.8%; intermediate-density lipoprotein, -44.7%; LDL, -46.1%). The number of VLDL apoB-100 particles secreted increased in response to the oral fat load. Despite this, total VLDL apoB-100 production over the 10-hour postprandial period was significantly decreased with ERN (-21.9%). In statin-treated men with type 2 diabetes mellitus, ERN decreased plasma Lp(a) concentrations by decreasing the production of apo(a) and Lp(a)-apoB-100. ERN also decreased the concentrations of apoB-100-containing lipoproteins by decreasing VLDL production and the transport of these particles down the VLDL to LDL cascade. Our study provides further mechanistic insights into the lipid-regulating effects of ERN. © 2015 American Heart Association, Inc.

  18. An update on gene therapy for the treatment of lipoprotein lipase deficiency

    Directory of Open Access Journals (Sweden)

    Libby AE

    2014-05-01

    Full Text Available Andrew E Libby, Hong Wang Division of Endocrinology, Metabolism, and Diabetes, School of Medicine, University of Colorado at Denver, Aurora, CO, USA Abstract: Lipoprotein lipase (LPL is responsible for clearance of triglyceride-rich lipoproteins from the blood. Deficiency or defects in this enzyme result in profound hypertriglyceridemia and susceptibility to chronic, life-threatening pancreatitis. Management of LPL deficiency has traditionally been restricted to palliative care and strategies to reduce the risk of pancreatitis, including severe dietary restrictions of fat. Recently, the European Commission approved the first gene therapy treatment in the West to treat this rare disease. Alipogene tiparvovec (Glybera® was granted marketing authorization in November 2012 to treat LPL deficiency in a subset of patients that are at increased risk for pancreatitis. Designed as a one-time treatment, the drug uses adeno-associated virus (AAV1 delivery of transgenic LPL to muscle in patients lacking functional enzyme. Although statistically significant reduction of serum triglycerides was initially observed in trial subjects, this effect was found to be transient, with triglyceride levels eventually rebounding to basal levels by 26 weeks in all participants. Nevertheless, despite the return of triglycerides to pretreatment levels, alipogene tiparvovec was found to have a long-term impact on postprandial chylomicron metabolism by lowering the fraction of triglyceride found in this subset of lipoproteins. Furthermore, the drug led to a clinically significant reduction in the incidence of pancreatitis in LPL-deficient patients. The regulatory approval of alipogene tiparvovec was a historic process and serves as an example of the challenges that future orphan drugs will face. Keywords: lipoprotein lipase deficiency, gene therapy, AAV, chylomicron, pancreatitis

  19. Effect of Different Dietary Oil Sources on Lipid Metabolism and Related Gene Expression in Broilers%饲粮不同油脂来源对肉鸡脂类代谢及相关基因表达的影响

    Institute of Scientific and Technical Information of China (English)

    倪红玉; 鲁菲; 温超; 吴大伟; 周岩民

    2011-01-01

    The trial was conducted to investigate the effect of different dietary oil sources on lipid metabolism and related gene expression in broilers. One hundred and sixty 1-day-old Arbor Acres (AA) broiler chickens with initial average body weight of (46. 00 ±0. 26) g were randomly divided into 2 groups with 10 replicates in each group and 8 chickens per replicate. Broilers were fed diets containing soybean oil or lard as oil sources, respectively. The trial lasted for 21 days. The results showed as follows; different dietary oil sources had no significant effects on triglyceride (TG), total cholesterol ( TC), high density lipoprotein cholesterol ( HDL-C) , low density lipoprotein cholesterol (LDL-C) and the ratio of HDL-C and LDL-C in serum of broilers at 21 days of age ( P > 0.05); the hepatic lipase ( HL) activity in serum of broilers in the soybean oil group was significantly higher than that in the lard group (P 0.05). The results indicate that soybean oil is more available for digestion and absorption of broilers, and it can reduce cholesterol synthesis and liver apoB mRNA expression level of boilers, while blood fat level and fatty acid synthesis can be slightly affected by oil sources.%本试验旨在探讨饲粮不同油脂来源对肉鸡脂类代谢及相关基因表达的影响.选取160只平均体重为(46.00±0.26)g的1日龄爱拔益加(AA)肉仔鸡随机分成2组,每组10个重复,每个重复8只鸡,分别饲喂油脂为豆油和猪油的饲粮.试验期为21 d.结果表明:饲粮不同油脂来源对21日龄肉鸡血清甘油三酯(TG)、总胆固醇(TC)、高密度脂蛋白胆固醇( HDL-C)、低密度脂蛋白胆固醇(LDL-C)含量和HDL-C/LDL-C比值均无显著影响(P>0.05);豆油组肉鸡血清肝脂酶(HL)活性极显著(P<0.01)高于猪油组,但血清脂蛋白脂酶(LPL)和总脂酶(TL)活性显著低于猪油组(P<0.05);豆油组肉鸡肝脏载脂蛋白B( apoB) mRNA表达量极显著低于猪油组(P<0.01),

  20. The effect of oat β-glucan on LDL-cholesterol, non-HDL-cholesterol and apoB for CVD risk reduction: a systematic review and meta-analysis of randomised-controlled trials.

    Science.gov (United States)

    Ho, Hoang V T; Sievenpiper, John L; Zurbau, Andreea; Blanco Mejia, Sonia; Jovanovski, Elena; Au-Yeung, Fei; Jenkins, Alexandra L; Vuksan, Vladimir

    2016-10-01

    Oats are a rich source of β-glucan, a viscous, soluble fibre recognised for its cholesterol-lowering properties, and are associated with reduced risk of CVD. Our objective was to conduct a systematic review and meta-analysis of randomised-controlled trials (RCT) investigating the cholesterol-lowering potential of oat β-glucan on LDL-cholesterol, non-HDL-cholesterol and apoB for the risk reduction of CVD. MEDLINE, Embase, CINAHL and Cochrane CENTRAL were searched. We included RCT of ≥3 weeks of follow-up, assessing the effect of diets enriched with oat β-glucan compared with controlled diets on LDL-cholesterol, non-HDL-cholesterol or apoB. Two independent reviewers extracted data and assessed study quality and risk of bias. Data were pooled using the generic inverse-variance method with random effects models and expressed as mean differences with 95 % CI. Heterogeneity was assessed by the Cochran's Q statistic and quantified by the I 2-statistic. In total, fifty-eight trials (n 3974) were included. A median dose of 3·5 g/d of oat β-glucan significantly lowered LDL-cholesterol (-0·19; 95 % CI -0·23, -0·14 mmol/l, PHDL-cholesterol (-0·20; 95 % CI -0·26, -0·15 mmol/l, PLDL-cholesterol (I 2=79 %) and non-HDL-cholesterol (I 2=99 %). Pooled analyses showed that oat β-glucan has a lowering effect on LDL-cholesterol, non-HDL-cholesterol and apoB. Inclusion of oat-containing foods may be a strategy for achieving targets in CVD reduction.

  1. The effect of long term under- and over-feeding on the expression of genes related to lipid metabolism in mammary tissue of sheep.

    Science.gov (United States)

    Tsiplakou, Eleni; Flemetakis, Emmanouil; Kouri, Evangelia-Diamanto; Sotirakoglou, Kyriaki; Zervas, George

    2015-02-01

    Milk fatty acid (FA) synthesis by the mammary gland involves expression of a large number of genes whose nutritional regulation remains poorly defined. In this study, we examined the effect of long-term under- and over-feeding on the expression of genes (acetyl Co A carboxylase, ACC; fatty acid synthetase, FAS; lipoprotein lipase, LPL; stearoyl Co A desaturase, SCD; peroxisome proliferator activated receptor γ2, PPARγ2; sterol regulatory element binding protein-1, SREBP-1c; and hormone sensitive lipase, HSL) related to FA metabolism in sheep mammary tissue (MT). Twenty-four lactating sheep were divided into three homogenous sub-groups and fed the same ration in quantities covering 70% (underfeeding), 100% (control) and 130% (overfeeding) of their energy and crude protein requirements. The results showed a significant reduction of mRNA of ACC, FAS, LPL and SCD in the MT of underfed sheep, and a significant increase on the mRNA of LPL and SREBP-1c in the MT of overfed compared with the control respectively. In conclusion, the negative, compared to positive, energy balance in sheep down-regulates ACC, FAS, LPL, SCD, SREBP-1c and PPARγ2 expression in their MT which indicates that the decrease in nutrient availability may lead to lower rates of lipid synthesis.

  2. 电针丰隆穴对高血脂症型地鼠肝脏LPL、HL的影响%Influence of Electro-acupuncture of Fenglong Point on Liver LPL and HL of Golden Hamsters with Hyperlipidemia

    Institute of Scientific and Technical Information of China (English)

    张红星; 王英淑; 周利; 杨金梅; 李璇; 王琼

    2011-01-01

    Objective: To investigate action mechanism of the electro-acupuncture of Fenglong point adjusting triglyceride in golden hamsters with hyperlipidemia. Methods: Thirty-two healthy male SPF golden hamsters were randomly divided into four groups (n=8 each): normal control group (ordinary diet), model control group (hyperlipidemia model established by high fat diet), electro-acupuncture group (after high fat diet for four weeks, electroacupuncture of fenglong point given); western medicine group (after high fat diet for four weeks, atorvastatin calcium given). After 4 weeks, TC, TG, LDL-C and HDL-C levels were compared between the normal control group and model control group; After 8 weeks, the fasting blood via the abdominal aorta and the liver tissues were collected in the electro-acupuncture group and western medicine group, and the liver LPL and HL activity was determined.Results: After high fat diet for 4 weeks, TC, TG and LDL-C levels in the model control group were significantly higher (P<0.05), while HDL-C levels were significantly lower than in the normal control group (P<0. 01), suggesting the successful construction of the hyperlipidemia model. After treatment for 8 weeks, LPL/HL activity was higher in electro-acupuncture group than in model control group ( P<0. 05 , P<0.01), but there was no significant difference between western medicine group and model control group. Conclusion: Electro-acupuncture of fenglong point can adjust the triglyceride metabolism in golden hamsters with hyperlipidemia probably by increasing the LPL and HL activity.%目的:探讨电针丰隆穴对调节高脂血症型金黄地鼠血脂的作用机制.方法:32只健康SPF级雄性金黄地鼠随机分为正常组8只,采用普通饲料喂养;模型组、电针组、西药组各8只,均采用高脂饲料喂养.1个月后电针组地鼠给予电针丰隆穴治疗;西药组给予阿托伐他汀钙灌胃,共治疗1个月.观察各组地鼠血清胆固醇(TC)、甘油三酯(TG)

  3. THE INFLUENCE OF APOLIPOPROTEIN B AND E GENE POLYMORPHISMS ON THE RESPONSE TO SIMVASTATIN THERAPY IN PATIENTS WITH HYPERLIPIDEMIA

    Institute of Scientific and Technical Information of China (English)

    叶平; 尚延忠; 丁小平

    2003-01-01

    Objective.To investigate the effect of apolipoprotein B(apoB)and E(apoE)genetic variations on lipid profile at baseline(before treatment),and also on the subsequent response to simvastatin therapy.Methods. Eighty-eight patients with hyperlipidemia were treated with simvastatin 5mg daily. The plasma levels of total cholesterol(TC)and low-density lipoprotein cholesterol(LDL-C),triglyceride(TG)and apo B were measured pretreatment and at the end of the 4th,8th and 12th post-treatment week.Polymorphisms of apoB at XbaI locus and apoE were determined by restriction fragment length polymorphism(RFLP).Results. In all patients,relative frequencies of X-allele and X+ allele were 0.943 and 0.057 for apoB gene respectively. For apoE gene the relative frequency of ε 2 allele was determined as 0.182,ε3 as 0.580 and ε4 as 0.238.The reduction in TC level was more prominent in patients carrying X- allele than in those with X+ allele following treatment(-23.9% vs. -13.6%,P< 0.05).Compared with patients carrying ε3 or ε4 allele,those with ε 2 allele showed a significantly higher percentage in reduction of apoB level after treatment(P< 0.05). Conclusion. The relative frequency of apoB X+ allele is high in patients with hyperlipidemia,in whom the TC-lowering efficacy is decreased following treatment of simvastatin. The relative frequencies of ε 2 and ε 4 are also high in hyperlipidemic patients,and the ε2 allele is associated with reduction in apoB level during lipid-regulating therapy.

  4. Coding Variation in ANGPTL4, LPL, and SVEP1 and the Risk of Coronary Disease

    DEFF Research Database (Denmark)

    Stitziel, Nathan O; Stirrups, Kathleen E; Masca, Nicholas G D

    2016-01-01

    BACKGROUND: The discovery of low-frequency coding variants affecting the risk of coronary artery disease has facilitated the identification of therapeutic targets. METHODS: Through DNA genotyping, we tested 54,003 coding-sequence variants covering 13,715 human genes in up to 72,868 patients with ...

  5. A lipoprotein lipase gene polymorphism interacts with consumption of alcohol and unsaturated fat to modulate serum HDL-cholesterol concentrations.

    Science.gov (United States)

    Baik, Inkyung; Lee, Seungku; Kim, Seong Hwan; Shin, Chol

    2013-10-01

    There are limited data from prospective studies regarding interactions between lipoprotein lipase gene (LPL) and lifestyle factors in association with HDL-cholesterol (HDL-C) concentrations, a biomarker of coronary heart disease risk. Our prospective cohort study investigated the interactive effects of a common LPL polymorphism and lifestyle factors, including obesity, smoking, alcohol consumption, physical activity, and dietary intake, on follow-up measurements of HDL-C and triglyceride (TG) concentrations. A total of 5314 Korean men and women aged 40-69 y participated in the study. Serum HDL-C and TG concentrations were measured in all participants at baseline and 6-y follow-up examinations. On the basis of genome-wide association data for HDL-C and TG concentrations, we selected the most significant polymorphism (rs10503669), which was in high linkage disequilibrium with the serine 447 stop (S447×) mutation (D' = 0.99) of LPL. We found that carrying the T allele reflecting the LPL ×447 allele was positively associated with follow-up measurement of HDL-C concentrations (P HDL-C concentration and potential risk factors, we observed interactive effects of the polymorphism and consumption of alcohol (P-interaction unsaturated fat (P-interaction HDL-C concentrations. We also observed interactive effects of the polymorphism and body mass index (P-interaction unsaturated fat to minimize reduction of blood HDL-C concentrations and that obese persons who do not carry the LPL ×447 allele need to control body weight to prevent hypertriglyceridemia.

  6. Effects of stocking density on lipid deposition and expression of lipid-related genes in Amur sturgeon (Acipenser schrenckii).

    Science.gov (United States)

    Ren, Yuanyuan; Wen, Haishen; Li, Yun; Li, Jifang; He, Feng; Ni, Meng

    2017-09-16

    To investigate the correlation between lipid deposition variation and stocking density in Amur sturgeon (Acipenser schrenckii) and the possible physiological mechanism, fish were conducted in different stocking densities (LSD 5.5 kg/m(3), MSD 8.0 kg/m(3), and HSD 11.0 kg/m(3)) for 70 days and then the growth index, lipid content, lipase activities, and the mRNA expressions of lipid-related genes were examined. Results showed that fish subjected to higher stocking density presented lower final body weights (FBW), specific growth ratio (SGR), and gonad adipose tissue index (GAI) (P density lipoprotein cholesterol (HDL-C) decreased significantly with increasing stocking density, while no significant change was observed for low-density lipoprotein cholesterol (LDL-C). Furthermore, the cDNAs encoding lipoprotein lipase (LPL) and hepatic lipase (HL) were isolated in Amur sturgeon, respectively. The full-length LPL cDNA was composed of 1757 bp with an open reading frame of 501 amino acids, while the complete nucleotide sequences of HL covered 1747 bp encoding 499 amino acids. In the liver, the activities and mRNA levels of LPL were markedly lower in HSD group, which were consistent with the variation tendency of HL. Fish reared in HSD group also presented lower levels of activities and mRNA expression of LPL in the muscle and gonad. Moreover, the expressions of peroxisome proliferator-activated receptor α (PPARα) in both the liver and skeletal muscle were significantly upregulated in HSD group. Overall, the results indicated that high stocking density negatively affects growth performance and lipid deposition of Amur sturgeon to a certain extent. The downregulation of LPL and HL and the upregulation of PPARα may be responsible for the lower lipid distribution of Amur sturgeon in higher stocking density.

  7. [Mutations of APOC3 gene, metabolism of triglycerides and reduction of ischemic cardiovascular events].

    Science.gov (United States)

    Pirillo, Angela; Catapano, Alberico Luigi

    2015-05-01

    A direct relationship between high plasma triglyceride (TG) levels and increased risk of cardiovascular disease has been shown in several studies. TG are present in the blood associated with different lipoprotein classes, including hepatically-derived very low density lipoproteins (VLDL) and intestinally-derived chylomicrons. Lipoprotein lipase (LPL) is a key enzyme that hydrolyzes TG, releasing free fatty acids that accumulate in peripheral tissues and remnant lipoproteins, that are then cleared by the liver. LPL activity is finely modulated by several cofactors, including apolipoprotein C-III (apoC-III) which acts as a LPL inhibitor. The key role of apoCIII has been established in several studies: animal models lacking APOC3 gene exhibit reduced plasma TG levels, whereas the overexpression of APOC3 gene led to increased TG levels. In humans, several mutations in APOC3 gene have been identified, leading to lower apoC-III levels and associated with reduced plasma TG levels. Recently, these mutations were found to be associated with a reduced risk for cardiovascular ischemia and coronary heart disease, thus confirming the negative role of apoC-III in TG metabolism and suggesting apoC-III as possible therapeutic target for the management of hypertriglyceridemia.

  8. The interferon-γ-mediated inhibition of lipoprotein lipase gene transcription in macrophages involves casein kinase 2- and phosphoinositide-3-kinase-mediated regulation of transcription factors Sp1 and Sp3

    OpenAIRE

    2008-01-01

    The mechanisms underlying transcriptional inhibition by interferon-γ (IFN-γ) are poorly understood despite the existence of a large number of genes that are regulated in this manner and the key role of this cytokine in inflammatory disorders such as atherosclerosis. We have previously identified a novel mechanism for transcriptional inhibition by IFN-γ that involves a reduction in the binding of transcription factors Sp1 and Sp3 to regulatory sequences in the lipoprotein lipase (LPL) gene. In...

  9. Gene

    Data.gov (United States)

    U.S. Department of Health & Human Services — Gene integrates information from a wide range of species. A record may include nomenclature, Reference Sequences (RefSeqs), maps, pathways, variations, phenotypes,...

  10. Polymorphism of rs1044925 in the acyl-CoA:cholesterol acyltransferase-1 gene and serum lipid levels in the Guangxi Bai Ku Yao and Han populations

    Directory of Open Access Journals (Sweden)

    Yan Ting-Ting

    2010-12-01

    Full Text Available Abstract Background The association of rs1044925 polymorphism in the acyl-CoA:cholesterol acyltransferase-1 (ACAT-1 gene and serum lipid profiles is not well known in different ethnic groups. Bai Ku Yao is a special subgroup of the Yao minority in China. The present study was carried out to clarify the association of rs1044925 polymorphism in the ACAT-1 gene and several environmental factors with serum lipid levels in the Guangxi Bai Ku Yao and Han populations. Methods A total of 626 subjects of Bai Ku Yao and 624 participants of Han Chinese were randomly selected from our previous stratified randomized cluster samples. Genotyping of rs1044925 polymorphism in the ACAT-1 gene was performed by polymerase chain reaction and restriction fragment length polymorphism combined with gel electrophoresis, and then confirmed by direct sequencing. Results The levels of serum total cholesterol (TC, high-density lipoprotein cholesterol (HDL-C, apolipoprotein (Apo AI and ApoB were lower in Bai Ku Yao than in Han (P P P P P P Conclusions These results suggest that the polymorphism of rs1044925 in the ACAT-1 gene is mainly associated with female serum TC, LDL-C and ApoB levels in the Bai Ku Yao population. The C allele carriers had lower serum TC, LDL-C and ApoB levels than the C allele noncarriers.

  11. Gene : CBRC-PMAR-01-0625 [SEVENS

    Lifescience Database Archive (English)

    Full Text Available CBRC-PMAR-01-0625 Novel UN D UNKNOWN APOB_HUMAN 0.0 28% emb|CAA28420.1| apo-B100 pr...TAQLQYAKNKEWHAVRLPVVPALHYAAERYRHVANAAFERYRDATLQWAREAYDDTRAMGADNLPKRFTVPGFTVPLLNMEVSPYTVELPDTSILVAQSYRTPRVYLPLVGYRVPSFELSLPRVNLPPM...WDVLKMDVTTKARDVQVLRAASSVEYTKNPNGYVLALPVMSEGNGYRVSIPEIRLRVPEFVKQIPAAIQAMLRDVFDSEVVGPPMPINIPAFRVPFIEMSLGPYTIDL...DNLAALFDFPEEFTVPAFRVPLFDVYVPAYTVRLWDITLPTVFMTQSFRVPFTSIVVSPYIIDLRNIQVPKMLRVPSFAFELPALPKIPM

  12. Association of BLV infection profiles with alleles of the BoLA-DRB3.2 gene.

    Science.gov (United States)

    Juliarena, M A; Poli, M; Sala, L; Ceriani, C; Gutierrez, S; Dolcini, G; Rodríguez, E M; Mariño, B; Rodríguez-Dubra, C; Esteban, E N

    2008-08-01

    Bovine leukaemia virus (BLV) causes lymphosarcoma and persistent lymphocytosis (PL). Some MHC class II gene polymorphisms have been associated with resistance and susceptibility to the development of lymphosarcoma and PL, as well as with a reduced number of circulating BLV-infected lymphocytes. Previously, 230 BLV-infected Holstein cattle were classified into two infection profiles characterized by low and high proviral loads (LPL and HPL respectively). Here, the influence of the polymorphism at the BoLA-DRB3.2* gene of these animals was examined. After genotyping, the association between the BoLA-DRB3.2* alleles and the BLV infection profile was determined as the odds ratio (OR). Two subtypes of allele *11 were identified (ISAG*0901 and *0902). Allele ISAG*0902 showed a stronger association with the LPL profile (OR = 8.24; P DRB3.2* alleles were assigned to three categories: resistant (R), susceptible (S) and neutral (N). Based on their DRB3 genotypes, cattle were classified as homozygous or heterozygous. The RR and RN genotypes were associated with the LPL profile, while the SS and NS genotypes were associated with the HPL profile. The RS genotype could not be associated with any particular profile. Our results show that allele ISAG*0902 appears to be the best BLV resistance marker in Holstein cattle.

  13. Genetic Variation of LPL Gene and Association Analysis with Meat Quality Traits in Bovine%牛LPL基因的遗传变异与肉品质性状的关联分析

    Institute of Scientific and Technical Information of China (English)

    郭艳青; 许尚忠; 孙宝忠; 高雪; 任红艳; 陈金宝

    2007-01-01

    脂蛋白脂酶(lipoprotein lipase,LPL)属于水解酶家族(Emmerichetal.,1992),是机体脂质和脂蛋白代谢的关键酶,是分解循环脂蛋白中乳糜微粒和极低密度脂蛋白中的甘油三酯,释放出脂肪酸和甘油的限速酶(Goldberg et al.,1980)。LPL在脂蛋白的运输过程和能量代谢方面发挥着重要作用。在猪、鸡等动物的研究上,将其作为影响背膘厚、肌间脂宽、腹脂重等性状的候选基因。有关牛的LPL基因多态性的研究报道较少。

  14. Fine mapping of the insulin-induced gene 2 identifies a variant associated with LDL cholesterol and total apolipoprotein B levels.

    Science.gov (United States)

    Do, Ron; Bailey, Swneke D; Paré, Guillaume; Montpetit, Alexandre; Desbiens, Katia; Hudson, Thomas J; Yusuf, Salim; Bouchard, Claude; Gaudet, Daniel; Pérusse, Louis; Anand, Sonia; Vohl, Marie-Claude; Pastinen, Tomi; Engert, James C

    2010-10-01

    In a whole-genome scan, a single nucleotide polymorphism (SNP) (rs7566605) upstream of the insulin-induced gene 2 (INSIG2) was shown to influence body mass index and obesity in the Framingham Heart Study, with replication of these results in an additional 4 of 5 studies. However, other studies could not replicate the association. Because INSIG2 plays an important role in cholesterol biosynthesis, we hypothesized that human INSIG2 variants might play a role in the regulation of plasma lipid and lipoprotein levels. We selected tagging SNPs spanning >100 kb of INSIG2 locus and sequenced 18 434 base pairs to discover novel SNPs. Thirty-two SNPs were genotyped in 645 individuals from the Quebec Family Study. Two SNPs (rs10490626 and rs12464355) were associated with plasma low-density lipoprotein cholesterol (LDL-C) (PJean, Quebec (P=0.040 for LDL-C, P=0.044 for apoB), 3247 Europeans (P=0.028 for LDL-C, P=0.030 for apoB), and 1695 South Asians (P=0.0036 for LDL-C, P=0.034 for apoB) from the INTERHEART study (for LDL-C, the combined 2-sided P=6.2×10⁻⁵ and for total apoB, P=0.0011). Furthermore, we identified a variant in the human sorbin and SH(3)-domain-containing-1 gene that was associated with INSIG2 mRNA levels, and this SNP was shown to act in combination with rs10490626 to affect LDL-C (P=0.022) in the Quebec Family Study and in INTERHEART South Asians (P=0.019) and Europeans (P=0.052). These results suggest that INSIG2 genetic variants may have a more direct role in lipid and lipoprotein metabolism than in obesity.

  15. 民猪脂蛋白脂酶基因在冷诱导后表达变化的研究%Study on Expression of Lipoprotein Lipase Gene in Min Pig during Cold Induced

    Institute of Scientific and Technical Information of China (English)

    张冬杰; 刘娣; 汪亮; 别墅; 孙洪涛; 杨国伟; 张海波

    2011-01-01

    脂蛋白脂酶(lipoprotein lipase,LPL)是动物分解代谢的限速酶,是影响脂肪代谢通路中的一个重要基因.本研究将LPL基因作为影响民猪抗寒特性的候选基因,对其在心脏、肝脏、胃、脾脏、肾脏、肺脏、大肠、小肠、子宫、卵巢、背肌、腿肌、脂肪共计13个组织内的表达情况和低温冷诱导后在民猪肌肉组织内的表达变化情况进行了分析.结果表明,LPL基因在所检测的13个组织中均有表达,但表达量存在差异,心脏、背肌、腿肌、脂肪组织中的表达量较高,子宫和卵巢组织的表达量较低;LPL基因在民猪被冷诱导后表达水平无显著变化.%Lipoprotein lipase (LPL) plays a central role in normal lipid metabolism as the key enzyme involved in the hydrolysis of triglycerides present in chylomicrons and very low density lipoproteins.In this research, LPL was seen as a candidate gene for cold resistance, analysis the expression of LPL in heart, liver, stomach, spleen, kidney, lung, large intestine,small intestin, uterus, ovary, muscles of back, leg muscle, fat tissues and during cold induced.The results showed that LPL was an abroad expression gene, but the level was different.It was higher expressed in heart, muscles of back, leg muscle and fat, but lower expressed in uterus, ovary.The expression level of LPL was not different after cold induced.

  16. Serum level of LOX-1 ligand containing ApoB is associated with increased carotid intima-media thickness in Japanese community-dwelling men, especially those with hypercholesterolemia LOX-1 ligand and IMT in Japanese.

    Science.gov (United States)

    Okamura, Tomonori; Miura, Katsuyuki; Sawamura, Tatsuya; Kadota, Aya; Hisamatsu, Takashi; Fujiyoshi, Akira; Miyamatsu, Naomi; Takashima, Naoyuki; Miyagawa, Naoko; Kadowaki, Takashi; Ohkubo, Takayoshi; Murakami, Yoshitaka; Nakamura, Yasuyuki; Ueshima, Hirotsugu

    2016-01-01

    The serum level of LOX-1 ligand containing ApoB (LAB) may reflect atherogenicity better than usual lipid parameters; however, the relationship between LAB and carotid intima-media thickness (IMT) was not clear even in Asian populations. A total of 992 community-dwelling Japanese men, aged 40 to 79 years, were enrolled in the present study. Serum LAB levels were measured by enzyme-linked immunosorbent assays (ELISAs) with recombinant LOX-1 and monoclonal anti-apolipoprotein B antibody. Serum LAB levels (median [interquartile range], μg cs/L) were 5341 μg cs/L (4093-7125). The mean average IMT of the common carotid artery was highest in the fourth LAB quartile (842 μm) compared with the first quartile (797 μm) after adjustment for age, high-density lipoprotein cholesterol, triglyceride, body mass index, hypertension, diabetes, high sensitivity C-reactive protein, smoking, and alcohol drinking. However, this statistically significant difference was lost after further adjustment for total cholesterol (TC). After stratification using the combination of median LAB and hypercholesterolemia (serum TC ≥ 6.21 mmol/L and/or lipid-lowering medication), the adjusted mean average IMT (standard error) in the high LAB/hypercholesterolemia group was 886 μm (12.7), 856 μm (16.7) in the low LAB/hypercholesterolemia group, and 833 μm (8.4) in the low LAB/normal cholesterol group (P = .004). After further adjustment for TC, mean average IMT in the high LAB group was significantly higher than that measured in the low LAB group in hypercholesterolemic participants not taking lipid-lowering medication. Serum LAB was associated with an increased carotid IMT in Japanese men, especially those with hypercholesterolemia. Copyright © 2016 National Lipid Association. Published by Elsevier Inc. All rights reserved.

  17. "FAMILIAL DEFECTIVE APOLIPORROTEIN B 100: FREQUENCY OF R3500Q MUTATION OF APOLIPOROTEIN B GENE IN IRANIAN HYPERCHOLESTEROLEMIC PATIENTS"

    Directory of Open Access Journals (Sweden)

    P. Fard-Esfahani

    2005-06-01

    Full Text Available Familial defective apolipoprotein (apo B 100 (FDB causes early-onset coronary heart diseases (CHD. It is produced by R3500Q mutation of the apoB gene resulting in decreased binding of LDL to LDL receptor. We screened the apo B gene for R3500Q mutation in 130 hypercholesterolemic patients, among whom 30 patients met criteria of familial hypercholesterolemia (FH. The prevalence of R3500Q allele in this patient population was 0%. To obtain better estimation of mutation frequency, a broad survey is needed.

  18. Effects of lipoprotein lipase gene variations, a high-carbohydrate low-fat diet, and gender on serum lipid profiles in healthy Chinese Han youth.

    Science.gov (United States)

    Huang, Xin; Gong, Renrong; Lin, Jia; Li, Ronghui; Xiao, Liying; Duan, Wei; Fang, Dingzhi

    2011-01-01

    A high-carbohydrate low-fat (HC/LF) diet and lipoprotein lipase gene (LPL) Ser447Stop and Hind III polymorphisms have separately been found to be associated with triacylglycerol (TG) and high density lipoprotein cholesterol (HDL-C). This study sought to test the effects of LPL polymorphisms and an HC/LF diet on the serum lipid profile of Chinese with a lower incidence of coronary artery disease (CAD) consuming a diet with less fat and more carbohydrates. Fifty-six healthy subjects (22.89 ± 1.80 years) were given a control diet of 30.1% fat and 54.1% carbohydrates for 7 days, followed by an HC/LF diet of 13.8% fat and 70.1% carbohydrate for 6 days; there were no changes in the fatty acid composition or restrictions on total energy. Serum lipid profiles at baseline, before and after the HC/LF diet, and LPL polymorphisms were analyzed. After 6 days of the HC/LF diet, TG and the homeostasis model assessment of insulin resistance (HOMAIR) index were found to increase only in females with S447S. No decrease in HDL-C was noted. In subjects with Hind III polymorphism, increased TG was found in all females but not in males. Increased HDL-C, together with apolipoprotein (apo) AI, was found in male H- carriers but not in males with H+/H+ and females. In conclusion, LPL Ser447Stop and Hind III polymorphisms modified the effects of an HC/LF diet on the serum lipid profiles of a young Chinese population in different ways. Effective strategies for dietary interventions targeted at younger populations should take into account the interplay between genetic polymorphisms, diet, and gender.

  19. Dietary conjugated linoleic acid modify gene expression in liver, muscles, and fat tissues of finishing pigs

    DEFF Research Database (Denmark)

    Tous, Nuria; Theil, Peter Kappel; Lauridsen, Charlotte

    2012-01-01

    in these tissues, except for SM intermuscular fat. Dietary CLA increased PPARγ in LT muscle (P fat. Transcription of genes related to FA synthesis was reduced by CLA in SM muscle and liver (SREBP1......, both P muscle and reduced (P increased (P muscle and intermuscular fat. Saturated FA were increased in all studied tissues (P ... (LPL), delta-6-desaturase (D6D), and stearoyl CoA desaturase (SCD) were determined by real-time PCR in longissimus thoracis (LT) and semimembranosus (SM) muscles, LT subcutaneous and SM intermuscular fat, and in the liver. Fatty acid (FA) composition was analyzed using gas chromatography...

  20. Identifying candidate driver genes by integrative ovarian cancer genomics data

    Science.gov (United States)

    Lu, Xinguo; Lu, Jibo

    2017-08-01

    Integrative analysis of molecular mechanics underlying cancer can distinguish interactions that cannot be revealed based on one kind of data for the appropriate diagnosis and treatment of cancer patients. Tumor samples exhibit heterogeneity in omics data, such as somatic mutations, Copy Number Variations CNVs), gene expression profiles and so on. In this paper we combined gene co-expression modules and mutation modulators separately in tumor patients to obtain the candidate driver genes for resistant and sensitive tumor from the heterogeneous data. The final list of modulators identified are well known in biological processes associated with ovarian cancer, such as CCL17, CACTIN, CCL16, CCL22, APOB, KDF1, CCL11, HNF1B, LRG1, MED1 and so on, which can help to facilitate the discovery of biomarkers, molecular diagnostics, and drug discovery.

  1. Studies on association between lipoprotein lipase gene polymorphisms of Pvu Ⅱ site and hypertriglyceridemics in Chinese

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    Objective To explore whether Pvu Ⅱ restriction fragment length polymorphisms (RFLP) in the lipoprotein lipase (LPL) gene are associated with hypertriglyceridemics (HTG).Methods Pvu Ⅱ restriction fragment length polymorphisms in the lipoprotein lipase gene on a sample of 135 HTG patients and 193 age-matched healthy individuals in Chengdu area were detected with the method of PCR-RFLP.Results The P+P+ genotype frequency and P+ allelic frequency of LPL gene for HTG cases are higher than those for control groups (0.460 vs 0.337, P<0.05; 0.689 vs 0.565, P<0.01). The serum levels of TG, apoC Ⅱ, apoC Ⅲ, apoE and TG/HDL-C in P+P+ genotype are higher than those in P-P- genotype (P<0.05).Conclusion The results suggest that P+P+ genotype in the lipoprotein lipase gene is associated with susceptibility to hypertriglyceridemics in Chinese population.

  2. Transgenetic Animal Model in Studying Blood Fat Metabolism%血脂类代谢研究中的转基因动物模型

    Institute of Scientific and Technical Information of China (English)

    卢笑丛; 王有为

    2003-01-01

    Transgenic animal model for diseases established to show diversified disease through the expression or excessiveexpression of gene. The lipid metabolizing is very a complex physiological process in human. During the gene-relating lipid metabolizing, it includes the factors of causing arteriosclerosis formed and the factors of reducing arteriosclerosis attack. This paper described the transgenic animal model and its characters of gene of aplipoprotein (Apo) such as ApoE,ApoA, ApoB, ApoC, receptor gene sweeping receptor SR-A, SR-B and SR-CD, gene of lipid metabolizing enzyme,gene of transprotein such as CETP, LPL etc. Those transgenic animal models play an important role in studying disease mechanism, drug screening, gene treatment and in producing the protein as drug using.

  3. Association of polymorphisms in genes involved in lipoprotein metabolism with plasma concentrations of remnant lipoproteins and HDL subpopulations before and after hormone therapy in postmenopausal women.

    Science.gov (United States)

    Lamon-Fava, Stefania; Asztalos, Bela F; Howard, Timothy D; Reboussin, David M; Horvath, Katalin V; Schaefer, Ernst J; Herrington, David M

    2010-02-01

    A high degree of inter-individual variability in plasma lipid level response to hormone therapy (HT) has been reported. Variations in the oestrogen receptor alpha gene (ESR1) and in genes involved in lipid metabolism may explain some of the variability in response to HT. Subjects Postmenopausal Caucasian women (n = 208) participating in a placebo-controlled randomized trial of 3.2 years of hormone therapy (HT). Plasma triglyceride (TG), remnant lipoprotein cholesterol (RLP-C), and high-density lipoprotein cholesterol (HDL-C) levels and HDL subpopulations were assessed at baseline and at follow up. Single nucleotide polymorphisms (SNPs) in ESR1 and in the ATP binding cassette A1 (ABCA1), cholesteryl ester transfer protein (CETP), hepatic lipase (LIPC), lipoprotein lipase (LPL), and scavenger receptor class B type I (SRB1) genes were assessed for their association with baseline plasma levels and HT-related changes in levels of RLP-C and HDL subpopulations. Carriers of the ESR1 PvuII or IVS1-1505 variants had lower plasma TG concentrations and higher plasma HDL-C and alpha-1 and prealpha-1 HDL particle levels at baseline and showed greater increases in HDL-C, apo A-I and alpha-1 particle levels after HT than wild-type carriers. Carriers of the N291S and D9N variants in the LPL gene had significantly higher remnant lipoproteins and lower alpha-2 HDL particle levels at baseline. The CETP TaqIB SNP was a significant determinant of baseline plasma HDL-C and HDL subpopulation profile. Single nucleotide polymorphisms in ESR1, CETP and LPL had significant effects on baseline plasma levels of TG-rich and HDL subpopulations. With the exception of ESR1 SNPs, variation in genes involved in lipid metabolism has a very modest effect on lipoprotein response to HT.

  4. Relative gene expression of fatty acid synthesis genes at 60 days postpartum in bovine mammary epithelial cells of Surti and Jafarabadi buffaloes

    Directory of Open Access Journals (Sweden)

    Mamta Janmeda

    2017-05-01

    Full Text Available Aim: Aim of the study was to study the relative gene expression of genes associated with fatty acid synthesis at 60 days postpartum (pp in bovine mammary epithelial cells (MECs of Surti and Jafarabadi buffaloes. Materials and Methods: A total of 10 healthy Surti and Jafarabadi buffaloes of each breed were selected at random from Livestock Research Station, Navsari and Cattle Breeding Farm, Junagadh, Gujarat, respectively, for this study. Milk sample was collected from each selected buffalo at day 60 pp from these two breeds to study relative gene expression of major milk fat genes using non-invasive approach of obtaining primary bovine MECs (pBMEC from milk samples. Results: In this study overall, the relative expression of the six major milk lipogenic genes butyrophilin subfamily 1 member A1 (BTN1A1, stearoyl-CoA desaturase (SCD, lipoprotein lipase (LPL, glycerol-3-phosphate acyltransferase mitochondrial (GPAM, acetyl-coenzyme A carboxylase alpha (ACACA, and lipin (LPIN did not show changes in expression patterns at 60th day of lactation in both Surti and Jafarabadi buffaloes. Conclusion: The pBMEC can be successfully recovered from 1500 ml of milk of Surti and Jafarabadi buffaloes using antibody-mediated magnetic bead separation and can be further used for recovering RNA for down step quantification of major milk lipogenic gene expression. The relative expression of the six major milk lipogenic genes BTN1A1, SCD, LPL, GPAM, ACACA, and LPIN did not show changes in expression patterns in both Surti and Jafarabadi buffaloes, suggesting expression levels of lipogenic genes are maintained almost uniform till peak lactation without any significant difference.

  5. Identification of variations of gene expression of visceral adipose and renal tissue in type 2 diabetic rats using cDNA representational difference analysis

    Institute of Scientific and Technical Information of China (English)

    杨架林; 李果; 张芳林; 刘优萍; 张迪; 周文中; 许光武; 杨义生; 罗敏

    2003-01-01

    Objectives To identify differences in gene expression in renal and visceral adipose tissue in type 2 diabetic rats using cDNA representational difference analysis (RDA) and to explore the molecular pathogenesis of type 2 diabetes and its chronic vascular complications.Methods A rat model of type 2 diabetes was generated by administration of a high fat and calorie diet combined with a low dose of streptozocin (STZ) injected into the tail vein. The difference bands were generated by cDNA representational difference analysis (cDNA RDA). The final difference products were ligated into the pUC-18 vector and sequenced. A bioformatics analysis was performed on the obtained expressed sequence tags (ESTs), and then the expression levels of known and novel genes were verified by semi-quantitative reverse transcription-PCR (RT-PCR). At the same time, full-length cDNA of a novel gene was cloned in silico.Results The type 2 diabetic rats in this experiment experienced hyperglycemia, lipidemia, lower insulin sensitivity and normal body weight. We obtained 9 novel ESTs and 2 novel genes from renal tissue of rats and 6 novel ESTs and 1 known gene, the rat lipoprotein lipase (LPL) gene from their visceral adipose tissue. The 2 novel genes (RS91 and RS2) from the renal tissue were both very similar to serine (or cysteine) proteinase inhibitor, clade F and eukaryotic translation initiation factor 3 and subunit 5 (EIF-3 epsilon). The expression of both novel genes and the LPL gene were upregulated in renal and visceral adipose tissue of type 2 diabetic and fat-enriched rats. Full-length cDNA of the novel gene RS91 was cloned in silico.Conclusions① The rat model of type 2 diabetes generated in this study was ideal because the disease in the animals closely mimicked type 2 diabetic patients ② cDNA RDA is a flexible, inexpensive, more accurate, sensitive and highly effective technique for identifying differences in gene expression ③ Six novel ESTs and 1 known gene were obtained

  6. Effect of short-term fasting and refeeding on transcriptional regulation of metabolic genes in human skeletal muscle.

    Science.gov (United States)

    Pilegaard, Henriette; Saltin, Bengt; Neufer, P Darrell

    2003-03-01

    During short-term fasting, substrate utilization in skeletal muscle shifts from predominantly carbohydrate to fat as a means of conserving glucose. To examine the potential influence of short-term fasting and refeeding on transcriptional regulation in skeletal muscle, muscle biopsies were obtained from nine male subjects at rest, after 20 h of fasting, and 1 h after consuming either a high-carbohydrate (CHO trial) or a low-carbohydrate (FAT trial) meal. Fasting induced an increase in transcription of the pyruvate dehydrogenase kinase 4 (PDK4) (10-fold), lipoprotein lipase (LPL) ( approximately 2-fold), uncoupling protein 3 (UCP3) ( approximately 5-fold), and carnitine palmitoyltransferase I (CPT I) ( approximately 2.5-fold) genes. Surprisingly, transcription of PDK4 and LPL increased further in response to refeeding (both trials) to more than 50-fold and 6- to 10-fold, respectively, over prefasting levels. However, responses varied among subjects with two subjects in particular displaying far greater activation of PDK4 (>100-fold) and LPL (>20-fold) than the other subjects (mean approximately 8-fold and approximately 2-fold, respectively). Transcription of UCP3 decreased to basal levels after the CHO meal but remained elevated after the FAT meal, whereas CPT I remained elevated after both refeeding meals. The present findings demonstrate that short-term fasting/refeeding in humans alters the transcription of several genes in skeletal muscle related to lipid metabolism. Marked heterogeneity in the transcriptional response to the fasting/refeeding protocol suggests that individual differences in genetic profile may play an important role in adaptive molecular responses to metabolic challenges.

  7. Effects of dietary energy level on lipid metabolism-related gene expression in subcutaneous adipose tissue of Yellow breed x Simmental cattle.

    Science.gov (United States)

    Zhang, Haibo; Zhang, Xiangfei; Wang, ZhiSheng; Dong, Xianwen; Tan, Cui; Zou, Huawei; Peng, Quanhui; Xue, Bai; Wang, Lizhi; Dong, Guozhong

    2015-04-01

    This study was conducted to estimate the effect of dietary energy level on lipid metabolism-related gene expression of subcutaneous adipose tissue in Yellow breed × Simmental cattle. The experiment was conducted for 60 days. The results showed that final weight, average daily gain, average backfat thickness, (testicles + kidney + pelvic) fat percentage and subcutaneous fat percentage in the high and medium energy groups were significantly higher than in the low-energy group but that the feed conversion ratio was significantly lower. The glucose, triglycerides, cholesterol, high-density lipoprotein and low-density lipoprotein in the high-energy group were significantly higher than in the low-energy group. With dietary energy increasing the activities of lipoprotein lipase (LPL), fatty acid synthase (FAS) and acetyl-CoA carboxylase (ACC) significantly increased, whereas hormone-sensitive lipase (HSL) and carnitine palmitoyltransferase-1 (CPT-1) significantly diminished. Peroxisome proliferator-activated receptor γ (PPARγ), LPL, FAS, sterol regulatory element binding protein 1 (SREBP-1), ACC, stearoyl-CoA desaturase (SCD) and adipocyte-fatty acid binding proteins (A-FABP) gene expression were significantly increased by dietary energy increasing, and HSL and CPT-1 gene expression were significantly decreased. These results indicated that with dietary energy increasing, the subcutaneous fat accumulation mainly increased due to adipose tissue lipogenic gene expression and decreased lipolytic gene expression.

  8. Gene Polymorphisms Affect the Effectiveness of Atorvastatin in Treating Ischemic Stroke Patients

    Directory of Open Access Journals (Sweden)

    Yun-Hua Yue

    2016-07-01

    Full Text Available Background/Aims: The aim of the present study is to investigate whether the single nucleotide polymorphism (SNP in lipid metabolism related genes would affect the effectiveness of atorvastatin in both Han and Uighur populations. Methods: 200 ischemic stroke patients were treated with atorvastatin. The differences of blood lipid level and their ratios were measured. Six lipid related genes, HMGCR, APOA5, LPL, CETP, LDLR and PCSK9 were selected as candidate genes. And nine SNP loci in these six genes were genotyped by SNaPshot technique. Results: In all patients treated with atorvastatin, the SNP rs662799 significantly affected the ratio of ΔLDL and ΔLDL/LDL (p < 0.05; the SNP rs320 significantly affected the ratio of ΔLDL/LDL and Δ(LDL/HDL/(LDL/HDL (p < 0.01 and the SNP rs708272 significantly affected the ratio of ΔLDL (p < 0.05. In Han population treated with atorvastatin, the SNP rs662799 significantly affected the ratio of ΔTG (p < 0.05; the SNP rs320 significantly affected the ratio of ΔLDL/LDL and Δ(LDL/HDL/(LDL/HDL (p < 0.01. In Uighur population treated with atorvastatin, the SNP rs2266788 significantly affected the ratio of ΔHDL (p < 0.05; the SNP rs662799 significantly affected the ratio of ΔLDL/LDL (p < 0.05 and the SNP rs708272 significantly affected the ratio of ΔLDL (p < 0.05. Conclusion: Polymorphisms of rs662799 and rs2266788 in APOA5 gene, rs320 in LPL gene and rs708272 in CETP gene had significant association with the effect of the lipid-lowering therapy via atorvastatin calcium on ischemic stroke patients.

  9. Chemotherapy Agents Alter Plasma Lipids in Breast Cancer Patients and Show Differential Effects on Lipid Metabolism Genes in Liver Cells.

    Science.gov (United States)

    Sharma, Monika; Tuaine, Jo; McLaren, Blair; Waters, Debra L; Black, Katherine; Jones, Lynnette M; McCormick, Sally P A

    2016-01-01

    Cardiovascular complications have emerged as a major concern for cancer patients. Many chemotherapy agents are cardiotoxic and some appear to also alter lipid profiles, although the mechanism for this is unknown. We studied plasma lipid levels in 12 breast cancer patients throughout their chemotherapy. Patients received either four cycles of doxorubicin and cyclophosphamide followed by weekly paclitaxel or three cycles of epirubicin, cyclophosphamide and 5'-fluorouracil followed by three cycles of docetaxel. Patients demonstrated a significant reduction (0.32 mmol/L) in high density lipoprotein cholesterol (HDL-C) and apolipoprotein A1 (apoA1) levels (0.18 g/L) and an elevation in apolipoprotein B (apoB) levels (0.15 g/L) after treatment. Investigation of the individual chemotherapy agents for their effect on genes involved in lipoprotein metabolism in liver cells showed that doxorubicin decreased ATP binding cassette transporter A1 (ABCA1) via a downregulation of the peroxisomal proliferator activated receptor γ (PPARγ) and liver X receptor α (LXRα) transcription factors. In contrast, ABCA1 levels were not affected by cyclophosphamide or paclitaxel. Likewise, apoA1 levels were reduced by doxorubicin and remained unaffected by cyclophosphamide and paclitaxel. Doxorubicin and paclitaxel both increased apoB protein levels and paclitaxel also decreased low density lipoprotein receptor (LDLR) protein levels. These findings correlate with the observed reduction in HDL-C and apoA1 and increase in apoB levels seen in these patients. The unfavourable lipid profiles produced by some chemotherapy agents may be detrimental in the longer term to cancer patients, especially those already at risk of cardiovascular disease (CVD). This knowledge may be useful in tailoring effective follow-up care plans for cancer survivors.

  10. Hepatic and subcutaneous adipose lipid metabolism genes modulation by dietary fish oil and stearate in transition goats

    Directory of Open Access Journals (Sweden)

    Greta Farina

    2015-07-01

    Full Text Available The objective of the experiment was to understand the interaction between saturated or unsaturated fatty acids and genes involved in lipid metabolism in liver and subcutaneous adipose tissue. With this purpose, further gene expression assays were performed on obtained adipose and liver samples from a previous in vivo study where expression levels of ADIPOQ, LPIN1, LPL, PPARG, SREBF1 and THRSP were already determined. The study consisted on the administration of either a no fat-supplemented, or a stearic acid or fish oil supplemented diets to dairy goats from the last week of gestation until 21 days after kidding. Fat-supplied goats received 30g/head/d extra fatty acids during the dry period and 50g/head/d during lactation. Liver and subcutaneous adipose tissue samples were harvested at day ­7, 7 and 21 relative to kidding and immediately snap frozen in liquid nitrogen. At the present moment, quantitative real-time RT-PCR of ACAT1, MSMO1, CPT1, IL6 on liver and ACACA, LEP, LPL, FASN, IL6 and PLIN2 on adipose tissue are running. Data obtained will be analysed using the MIXED procedure of SAS and results may increase the knowledge on the mechanism of action of saturated or unsaturated dietary fatty acid sources in the fatty acid metabolism changes during transition in dairy goats.

  11. Exercise attenuates the fasting-induced transcriptional activation of metabolic genes in skeletal muscle.

    Science.gov (United States)

    Hildebrandt, A L; Neufer, P D

    2000-06-01

    Fasting elicits a progressive increase in lipid metabolism within skeletal muscle. To determine the effects of fasting on the transcriptional regulation of genes important for metabolic control in skeletal muscle composed of different fiber types, nuclei from control and fasted (24 and 72 h) rats were subjected to nuclear run-on analysis using an RT-PCR-based technique. Fasting increased (P < 0.05) transcription rate of the muscle-specific uncoupling protein-3 gene (UCP3) 14.3- to 21.1-fold in white gastrocnemius (WG; fast-twitch glycolytic) and 5.5- to 7.5-fold in red gastrocnemius (RG; fast-twitch oxidative) and plantaris (PL; mixed) muscles. No change occurred in soleus (slow-twitch oxidative) muscle. Fasting also increased transcription rate of the lipoprotein lipase (LPL), muscle carnitine palmitoyltransferase I (CPT I), and long-chain acyl-CoA dehydrogenase (LCAD) genes 1.7- to 3.7-fold in WG, RG, and PL muscles. Transcription rate responses were similar after 24 and 72 h of fasting. Surprisingly, increasing metabolic demand during the initial 8 h of starvation (two 2-h bouts of treadmill running) attenuated the 24-h fasting-induced transcriptional activation of UCP3, LPL, CPT I, and LCAD in RG and PL muscles, suggesting the presence of opposing regulatory mechanisms. These data demonstrate that fasting elicits a fiber type-specific coordinate increase in the transcription rate of several genes involved in and/or required for lipid metabolism and indicate that exercise may attenuate the fasting-induced transcriptional activation of specific metabolic genes.

  12. Association of the D8S282 marker near the lipoprotein lipase gene locus with systolic blood pressure in healthy Chinese subjects.

    Science.gov (United States)

    Ma, Yan-Qing; Thomas, G Neil; Critchley, Julian A J H; Lee, Zoe S K; Chan, Juliana C N; Tomlinson, Brian

    2002-11-01

    To investigate the association between the marker D8S282 near the lipoprotein lipase (LPL) gene locus, and blood pressure, anthropometric and biochemical parameters in 229 healthy Chinese subjects. METHOD Genotyping was performed using an automated DNA sequencer and the Base ImageIR software. Eight different alleles were identified (272-286 bp) resulting in 15 genotypes in our population. We investigated the association between the common (28.8%) 278 bp allele and the anthropometric and biochemical parameters. In a tertile analysis, the frequency of the 278 bp allele increased linearly ( P = 0.003) with increasing systolic blood pressure (SBP). The relationship was most evident in the females ( n = 141); SBP was higher in homozygotes for the 278 bp allele (117 +/- 10 mmHg, = 12) than those without this allele (109 +/- 9 mmHg, = 77, 0.05) and was gene-dose dependent, and this difference was more significant after adjusting for age (P = 0.004). No relationship between the locus and the anthropometric or biochemical parameters investigated was observed. The D8S282 marker near the LPL gene locus contributes to the variance of SBP in healthy Hong Kong Chinese subjects, particularly in females.

  13. Hydroxytyrosol Inhibits Cannabinoid CB1 Receptor Gene Expression in 3T3-L1 Preadipocyte Cell Line.

    Science.gov (United States)

    Tutino, Valeria; Orlando, Antonella; Russo, Francesco; Notarnicola, Maria

    2016-02-01

    The 3T3-L1 preadipocyte cell line is a well characterized cell model for studying the adipocyte status and the molecular mechanisms involved in differentiation of these cells. 3T3-L1 preadipocytes have the ability to synthesize and degrade endocannabinoid anandamide (AEA) and their differentiation into adipocytes increases the expression of cannabinoid (CB1) and PPAR-γ receptors. Clinically, the blocking stimulation of the endocannabinoid pathway has been one of the first approaches proposed to counteract the obesity and obesity-associated diseases (such as diabetes, metabolic syndrome and cancer). In this connection, here we studied in cultured 3T3-L1 pre-adipocytes the effects of n-3-PUFA, α-Linolenic acid (OM-3), n-6-PUFA, Linoleic acid (OM-6), and hydroxytyrosol (HT) on the expression of CB1 receptor gene and the adipogenesis-related genes PPAR-γ, Fatty Acid Synthase (FAS) and Lipoprotein Lipase (LPL). HT was able to inhibit 3T3-L1 cell differentiation by down-regulating cell proliferation and CB1 receptor gene expression. HT exhibited anti-adipogenic effects, whereas OM-3 and OM-6 exerted an inhibitory action on cell proliferation associated with an induction of the preadipocytes differentiation and CB1 receptor gene expression. Moreover, the expression of FAS and LPL genes resulted increased after treatment with both HT and OM-3 and OM-6. The present study points out that the intake of molecules such as HT, contained in extra virgin olive oil, may be considered also in view of antiobesity and antineoplastic properties by acting directly on the adipose tissue and modulating CB1 receptor gene transcription.

  14. Gene network and pathway analysis of bovine mammary tissue challenged with Streptococcus uberis reveals induction of cell profileration and inhibition of PPARγ signaling as potential mechanism for the negative relationships between immune response and lipid metabolism

    DEFF Research Database (Denmark)

    Moyes, Kasey M; Drackley, James K; Morin, Dawn E

    2009-01-01

    , and decrease economic losses to dairy farmers. The main objective of this study was to determine the most affected gene networks and pathways in mammary tissue in response to an intramammary infection (IMI) with S. uberis and relate these with other physiological measurements associated with immune and....../or metabolic responses to mastitis challenge with S. uberis O140J. Results Streptococcus uberis IMI resulted in 2,102 (1,939 annotated) differentially expressed genes (DEG). Within this set of DEG, we uncovered 20 significantly enriched canonical pathways (with 20 to 61 genes each), the majority of which were...... primarily involved with the immune response, e.g., IL6, TNF, IL8, IL10, SELL, LYZ, and SAA3. Genes down-regulated (1,020) included those associated with milk fat synthesis, e.g., LPIN1, LPL, CD36, and BTN1A1. Network analysis of DEG indicated that TNF had positive relationships with genes involved...

  15. Association of COMT gene polymorphisms with cerebral infarction in Han people of Tianjin

    Directory of Open Access Journals (Sweden)

    WANG Jin-huan

    2013-04-01

    Full Text Available Background Catechol-O-methyltransferase (COMT has a key function in thedegradation of catecholamines and inactivating estrogen. A common polymorphism in the COMT gene is guanine-adenine (G-A point mutation on rs4680, which causes a valine (Val substitution to methionine (Met in 108 and (or 158 amino acid by this gene and is responsible for lowered activity of the enzyme. The Val/Met polymorphism has been recognized to be associated with psychiatric disorders, alcohol dependence and drug side effects, but few study has been done to examine the relationship with cerebral infarction (CI. The objective of this study is to investigate the relationship between the polymorphisms of COMT gene and CI. Methods The polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP was used to detect COMT Val158Met genotype in 181 CI patients and 148 cases of controls. Meanwhile the serum levels of glucose, total cholesterol (TC, triglyceride (TG, low-density lipoprotein cholesterol (LDL-C , high-density lipoprotein cholesterol (HDL-C , apolipoprotein B (ApoB and ApoA in CI group were detected. Results The frequency of Val allele (78.45% and Val/Valgenotype (61.33% in CI was significantly higher than that in the control group (68.24% and 45.95%, P 0.05 than that in the control group. The serum levels of glucose, TC, TG, LDL-C, HDL-C, ApoB, ApoA and the frequency of hypertension had no difference between Val/Val genotype and Val/Met + Met/Met genotypes ( P > 0.05, for all. Conclusion The frequencies of Val allele and Val/Val genotype can be considered as genetic risk factors of male CI patients. The effect of COMT on CI is not related to blood pressure, serum lipid and glucose.

  16. The age dependency of gene expression for plasma lipids, lipoproteins, and apolipoproteins

    Energy Technology Data Exchange (ETDEWEB)

    Snieder, H.; Doornen, L.J.P. van; Boomsma, D.I. [Vrije Universiteit, Amsterdam (Netherlands)

    1997-03-01

    The aim of this study was to investigate and disentangle the genetic and nongenetic causes of stability and change in lipids and (apo)lipoproteins that occur during the lifespan. Total cholesterol, low-density lipoprotein (LDL), high-density lipoprotein (HDL), triglycerides, apolipoprotein A1 (ApoA1), apolipoprotein B (ApoB), and lipoprotein(a) (Lp[a]) were measured in a group of 160 middle-aged parents and their twin offspring (first project) and in a group of 203 middle-aged twin pairs (second project). Combining the data of both projects enabled the estimation of the extent to which measured lipid parameters are influenced by different genes in adolescence and adulthood. To that end, an extended quantitative genetic model was specified, which allowed the estimation of heritabilities for each sex and generation separately. Heritabilities were similar for both sexes and both generations. Larger variances in the parental generation could be ascribed to proportional increases in both unique environmental and additive genetic variance from childhood to adulthood, which led to similar heritability estimates in adolescent and middle-aged twins. Although the magnitudes of heritabilities were similar across generations, results showed that, for total cholesterol, triglycerides, HDL, and LDL, partly different genes are expressed in adolescence compared to adulthood. For triglycerides, only 46% of the genetic variance was common to both age groups; for total cholesterol this was 80%. Intermediate values were found for HDL (66%) and LDL (76%). For ApoA1, ApoB, and Lp(a), the same genes seem to act in both generations. 56 refs., 2 figs., 5 tabs.

  17. Multiple Genome Comparison within a Bacterial Species Reveals a Unit of Evolution Spanning Two Adjacent Genes in a Tandem Paralog Cluster

    Science.gov (United States)

    Tsuru, Takeshi

    2008-01-01

    It has been assumed that an open reading frame (ORF) represents a unit of gene evolution as well as a unit of gene expression and function. In the present work, we report a case in which a unit comprising the 3′ region of an ORF linked to a downstream intergenic region that is in turn linked to the 5′ region of a downstream ORF has been conserved, and has served as the unit of gene evolution. The genes are tandem paralogous genes from the bacterium Staphylococcus aureus, for which more than ten entire genomes have been sequenced. We compared these multiple genome sequences at a locus for the lpl (lipoprotein-like) cluster (encoding lipoprotein homologs presumably related to their host interaction) in the genomic island termed νSaα. A highly conserved nucleotide sequence found within every lpl ORF is likely to provide a site for homologous recombination. Comparison of phylogenies of the 5′-variable region and the 3′-variable region within the same ORF revealed significant incongruence. In contrast, pairs of the 3′-variable region of an ORF and the 5′-variable region of the next downstream ORF gave more congruent phylogenies, with distinct groups of conserved pairs. The intergenic region seemed to have coevolved with the flanking variable regions. Multiple recombination events at the central conserved region appear to have caused various types of rearrangements among strains, shuffling the two variable regions in one ORF, but maintaining a conserved unit comprising the 3′-variable region, the intergenic region, and the 5′-variable region spanning adjacent ORFs. This result has strong impact on our understanding of gene evolution because most gene lineages underwent tandem duplication and then diversified. This work also illustrates the use of multiple genome sequences for high-resolution evolutionary analysis within the same species. PMID:18765438

  18. PPARα signal pathway gene expression is associated with fatty acid content in yak and cattle longissimus dorsi muscle.

    Science.gov (United States)

    Qin, W; Liang, C N; Guo, X; Chu, M; Pei, J; Bao, P J; Wu, X Y; Li, T K; Yan, P

    2015-11-19

    Intramuscular fatty acid (FA) is related to meat qualities such as juiciness, tenderness, palatability, and shear force. PPARα plays an important role in lipid metabolism in the liver and skeletal muscle. This study investigated FA composition in yaks and cattle, in order to ascertain whether a correlation between PPARα signal pathway genes as candidate genes and meat FA composition in yaks and cattle exists. Statistical analyses revealed that levels of monounsaturated fatty acid (MUFA) and polyunsaturated fatty acid (PUFA) in yaks were significantly higher than those in cattle (P cattle (P cattle. However, LPL expression in yaks was significantly higher than that in cattle (P cattle, the mRNA level of PLTP was positively correlated with SFA (P meat quality.

  19. High-resolution genetic mapping in the diversity outbred mouse population identifies Apobec1 as a candidate gene for atherosclerosis.

    Science.gov (United States)

    Smallwood, Tangi L; Gatti, Daniel M; Quizon, Pamela; Weinstock, George M; Jung, Kuo-Chen; Zhao, Liyang; Hua, Kunjie; Pomp, Daniel; Bennett, Brian J

    2014-10-23

    Inbred mice exhibit strain-specific variation in susceptibility to atherosclerosis and dyslipidemia that renders them useful in dissecting the genetic architecture of these complex diseases. Traditional quantitative trait locus (QTL) mapping studies using inbred strains often identify large genomic regions, containing many genes, due to limited recombination and/or sample size. This hampers candidate gene identification and translation of these results into possible risk factors and therapeutic targets. An alternative approach is the use of multiparental outbred lines for genetic mapping, such as the Diversity Outbred (DO) mouse panel, which can be more informative than traditional two-parent crosses and can aid in the identification of causal genes and variants associated with QTL. We fed 292 female DO mice either a high-fat, cholesterol-containing (HFCA) diet, to induce atherosclerosis, or a low-fat, high-protein diet for 18 wk and measured plasma lipid levels before and after diet treatment. We measured markers of atherosclerosis in the mice fed the HFCA diet. The mice were genotyped on a medium-density single-nucleotide polymorphism array and founder haplotypes were reconstructed using a hidden Markov model. The reconstructed haplotypes were then used to perform linkage mapping of atherosclerotic lesion size as well as plasma total cholesterol, triglycerides, insulin, and glucose. Among our highly significant QTL we detected a ~100 kb QTL interval for atherosclerosis on Chromosome 6, as well as a 1.4 Mb QTL interval on Chromosome 9 for triglyceride levels at baseline and a coincident 22.2 Mb QTL interval on Chromosome 9 for total cholesterol after dietary treatment. One candidate gene within the Chromosome 6 peak region associated with atherosclerosis is Apobec1, the apolipoprotein B (ApoB) mRNA-editing enzyme, which plays a role in the regulation of ApoB, a critical component of low-density lipoprotein, by editing ApoB mRNA. This study demonstrates the value

  20. Genes and Gene Therapy

    Science.gov (United States)

    ... correctly, a child can have a genetic disorder. Gene therapy is an experimental technique that uses genes to ... or prevent disease. The most common form of gene therapy involves inserting a normal gene to replace an ...

  1. Differential induction of enzymes and genes involved in lipid metabolism in liver and visceral adipose tissue of juvenile yellow catfish Pelteobagrus fulvidraco exposed to copper

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Qi-Liang; Luo, Zhi, E-mail: luozhi99@yahoo.com.cn; Pan, Ya-Xiong; Zheng, Jia-Lang; Zhu, Qing-Ling; Sun, Lin-Dan; Zhuo, Mei-Qin; Hu, Wei

    2013-07-15

    Highlights: •Cu downregulates lipogenesis and reduces lipid deposition in liver and adipose tissue. •Mechanism of Cu affecting lipid metabolism is determined at the enzymatic and molecular levels. •Cu exposure differentially influences lipid metabolism between liver and adipose tissue. -- Abstract: The present study was conducted to determine the mechanism of waterborne Cu exposure influencing lipid metabolism in liver and visceral adipose tissue (VAT) of juvenile yellow catfish Pelteobagrus fulvidraco. Yellow catfish were exposed to four waterborne copper (Cu) concentrations (2 (control), 24 (low), 71 (medium), 198 (high) μg Cu/l, respectively) for 6 weeks. Waterborne Cu exposure had a negative effect on growth and several condition indices (condition factor, viscerosomatic index, hepatosomatic index and visceral adipose index). In liver, lipid content, activities of lipogenic enzymes (6-phosphogluconate dehydrogenase (6PGD), glucose-6-phosphate dehydrogenase (G6PD), malic enzyme (ME), isocitrate dehydrogenase (ICDH), and fatty acid synthase (FAS)) as well as mRNA levels of 6PGD, G6PD, FAS and sterol-regulator element-binding protein-1 (SREBP-1) genes decreased with increasing Cu concentrations. However, activity and mRNA level of lipoprotein lipase (LPL) gene in liver increased. In VAT, G6PD, ME and LPL activities as well as the mRNA levels of FAS, LPL and PPARγ genes decreased in fish exposed to higher Cu concentrations. The differential Pearson correlations between transcription factors (SREBP-1 and peroxisome proliferators-activated receptor-γ (PPARγ)), and the activities and mRNA expression of lipogenic enzymes and their genes were observed between liver and VAT. Thus, our study indicated that reduced lipid contents in liver and VAT after Cu exposure were attributable to the reduced activities and mRNA expression of lipogenic enzymes and their genes in these tissues. Different response patterns of several tested enzymes and genes to waterborne Cu

  2. A systematic evaluation of short tandem repeats in lipid candidate genes: riding on the SNP-wave.

    Directory of Open Access Journals (Sweden)

    Claudia Lamina

    Full Text Available Structural genetic variants as short tandem repeats (STRs are not targeted in SNP-based association studies and thus, their possible association signals are missed. We systematically searched for STRs in gene regions known to contribute to total cholesterol, HDL cholesterol, LDL cholesterol and triglyceride levels in two independent studies (KORA F4, n = 2553 and SAPHIR, n = 1648, resulting in 16 STRs that were finally evaluated. In a combined dataset of both studies, the sum of STR alleles was regressed on each phenotype, adjusted for age and sex. The association analyses were repeated for SNPs in a 200 kb region surrounding the respective STRs in the KORA F4 Study. Three STRs were significantly associated with total cholesterol (within LDLR, the APOA1/C3/A4/A5/BUD13 gene region and ABCG5/8, five with HDL cholesterol (3 within CETP, one in LPL and one inAPOA1/C3/A4/A5/BUD13, three with LDL cholesterol (LDLR, ABCG5/8 and CETP and two with triglycerides (APOA1/C3/A4/A5/BUD13 and LPL. None of the investigated STRs, however, showed a significant association after adjusting for the lead or adjacent SNPs within that gene region. The evaluated STRs were found to be well tagged by the lead SNP within the respective gene regions. Therefore, the STRs reflect the association signals based on surrounding SNPs. In conclusion, none of the STRs contributed additionally to the SNP-based association signals identified in GWAS on lipid traits.

  3. A Systematic Evaluation of Short Tandem Repeats in Lipid Candidate Genes: Riding on the SNP-Wave

    Science.gov (United States)

    Lamina, Claudia; Haun, Margot; Coassin, Stefan; Kloss-Brandstätter, Anita; Gieger, Christian; Peters, Annette; Grallert, Harald; Strauch, Konstantin; Meitinger, Thomas; Kedenko, Lyudmyla; Paulweber, Bernhard; Kronenberg, Florian

    2014-01-01

    Structural genetic variants as short tandem repeats (STRs) are not targeted in SNP-based association studies and thus, their possible association signals are missed. We systematically searched for STRs in gene regions known to contribute to total cholesterol, HDL cholesterol, LDL cholesterol and triglyceride levels in two independent studies (KORA F4, n = 2553 and SAPHIR, n = 1648), resulting in 16 STRs that were finally evaluated. In a combined dataset of both studies, the sum of STR alleles was regressed on each phenotype, adjusted for age and sex. The association analyses were repeated for SNPs in a 200 kb region surrounding the respective STRs in the KORA F4 Study. Three STRs were significantly associated with total cholesterol (within LDLR, the APOA1/C3/A4/A5/BUD13 gene region and ABCG5/8), five with HDL cholesterol (3 within CETP, one in LPL and one inAPOA1/C3/A4/A5/BUD13), three with LDL cholesterol (LDLR, ABCG5/8 and CETP) and two with triglycerides (APOA1/C3/A4/A5/BUD13 and LPL). None of the investigated STRs, however, showed a significant association after adjusting for the lead or adjacent SNPs within that gene region. The evaluated STRs were found to be well tagged by the lead SNP within the respective gene regions. Therefore, the STRs reflect the association signals based on surrounding SNPs. In conclusion, none of the STRs contributed additionally to the SNP-based association signals identified in GWAS on lipid traits. PMID:25050552

  4. Studies of Influences of Blood Glucose Controlling on the Changes of Lipid Profiles, ApoB100, ApoAI and HDL Subclass of Newly Diagnosed Type 2 Diabetes%血糖控制对新诊断的2型糖尿病患者血脂、ApoB100、ApoAI及HDL亚类影响的研究

    Institute of Scientific and Technical Information of China (English)

    陶世冰; 田丽; 傅明德; 田浩明

    2013-01-01

    本研究目的是探讨血糖控制对新诊断糖尿病患者血脂、载脂蛋白B100 (ApoB100)、ApoAI及高密度脂蛋白(HDL)亚类代谢的影响.53名新诊断的2型糖尿病患者分为4组,分别为单纯饮食和运动干预组(,n=13),口服降糖药组(n=13),胰岛素多次皮下注射强化治疗组(MDI)(n=13),胰岛素泵强化治疗组(CSII)(n=14).所有受试者均进行一个月的血糖控制治疗.分别检测受试者入组及干预结束时的空腹血糖(FPG)、糖化血红蛋白(HbA1C)、血脂、ApoB100和ApoAI,采用双向电泳免疫印迹的方法测定血浆HDL亚类的含量.共43名受试者完成该试验,结果表明:①降血糖治疗结束时,各组受试者的FPG、HbA1c、甘油三酯(TG)、总胆固醇(TC)、低密度脂蛋白胆固醇(LDL-C)、ApoB100的水平均明显降低,ApoAI/ApoB100比值则显著升高,而高密度脂蛋白胆固醇(HDL-C)/ApoAI、LDL-C/ApoB100无明显变化.此外,通过降血糖治疗后的受试者其血浆成熟的、大颗粒的HDL2b的含量增加,并且小颗粒的HDL3b的含量则有所下降.②单纯饮食运动组血脂及载脂蛋白改善作用不显著;但降糖药物治疗组的TC、LDL-C、ApoB100水平明显降低,ApoAI/B100比值和HDL2b的含量明显升高.③特别是在胰岛素强化治疗组(MDI、CSII),ApoB100水平的下降尤为明显.通过对新诊断的2型糖尿病患者血糖的严格控制可使患者血脂水平、ApoAI、ApoB100出现不同程度的改善,并可以使HDL亚类中相对成熟的成分增加,同时使其相对幼稚的成份减少.%This study was aimed to observe if the lipid profiles, apoprotein B100 (ApoB100) . ApoAI, high density lip-oprotein (HDL) and its subclasses could be improved by controlling the blood glucose. Fifty-three patients with newly diagnosed type 2 diabetic were divided into four groups: diet and exercise group (n=13), continuous subcutaneous insulin infusion (CSII) group (n=14), multiple daily insulin injection group (MDI, n=13

  5. Association of TNF-α gene promoter region polymorphisms in bovine leukemia virus (BLV)-infected cattle with different proviral loads.

    Science.gov (United States)

    Lendez, Pamela Anahi; Passucci, Juan Antonio; Poli, Mario Andres; Gutierrez, Silvina Elena; Dolcini, Guillermina Laura; Ceriani, Maria Carolina

    2015-08-01

    Tumor necrosis factor alpha (TNF-α) is a pleiotropic cytokine involved in the immune response against viral and other infections. Its expression levels are affected by a polymorphism in the promoter region of the gene. Bovine leukemia virus is a retrovirus that infects cattle and develops two different infection profiles in the host. One profile is characterized by a high number of proviral copies integrated into the host genome and a strong immune response against the virus, while the most relevant property of the other profile is that the number of copies integrated into the host genome is almost undetectable and the immune response is very weak. We selected a population of cattle sufficiently large for statistical analysis and classified them according to whether they had a high or low proviral load (HPL or LPL). Polymorphisms in the promoter region were identified by PCR-RFLP. The results indicated that, in the HPL group, the three possible genotypes were normally distributed and that, in the LPL group, there was a significant association between the proviral load and a low frequency of the G/G genotype at position -824.

  6. Associations of lipoprotein lipase gene rs326 with changes of lipid profiles after a high-carbohydrate and low-fat diet in healthy Chinese Han youth.

    Science.gov (United States)

    Zhu, Xing-chun; Lin, Jia; Wang, Qian; Liu, Hui; Qiu, Li; Fang, Ding-zhi

    2014-04-23

    To investigate the effects of a high-carbohydrate and low-fat (HC/LF) diet on plasma lipids and apolipoproteins (Apos) of healthy Chinese Han youth with different genotypes of lipoprotein lipase gene (LPL) rs326, 56 subjects were given a washout diet of 30.1% fat and 54.1% carbohydrate for seven days, followed by the HC/LF diet of 13.8% fat and 70.1% carbohydrate for six days, with no total energy restriction. Plasma glucose, triglyceride (TG), total cholesterol (TC), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), Apo B-100 and Apo A-I were analyzed at baseline and before and after the HC/LF diet. The results show that, when compared with before the HC/LF diet, only the male G carriers experienced increased HDL-C (p = 0.008) and Apo A-I (p = 0.005) after the HC/LF diet. Decreased TC in both males and females and increased TG in females were found regardless of the genotype after the HC/LF diet. LDL-C decreased in all the subjects although the decrease was not significant in the female G carriers. These results demonstrate that the G allele of LPL rs326 associates with the elevated levels of HDL-C and Apo A-I after the HC/LF diet in males of the healthy Chinese Han Youth.

  7. Associations of Lipoprotein Lipase Gene rs326 with Changes of Lipid Profiles after a High-Carbohydrate and Low-Fat Diet in Healthy Chinese Han Youth

    Directory of Open Access Journals (Sweden)

    Xing-chun Zhu

    2014-04-01

    Full Text Available To investigate the effects of a high-carbohydrate and low-fat (HC/LF diet on plasma lipids and apolipoproteins (Apos of healthy Chinese Han youth with different genotypes of lipoprotein lipase gene (LPL rs326, 56 subjects were given a washout diet of 30.1% fat and 54.1% carbohydrate for seven days, followed by the HC/LF diet of 13.8% fat and 70.1% carbohydrate for six days, with no total energy restriction. Plasma glucose, triglyceride (TG, total cholesterol (TC, high density lipoprotein cholesterol (HDL-C, low density lipoprotein cholesterol (LDL-C, Apo B-100 and Apo A-I were analyzed at baseline and before and after the HC/LF diet. The results show that, when compared with before the HC/LF diet, only the male G carriers experienced increased HDL-C (p = 0.008 and Apo A-I (p = 0.005 after the HC/LF diet. Decreased TC in both males and females and increased TG in females were found regardless of the genotype after the HC/LF diet. LDL-C decreased in all the subjects although the decrease was not significant in the female G carriers. These results demonstrate that the G allele of LPL rs326 associates with the elevated levels of HDL-C and Apo A-I after the HC/LF diet in males of the healthy Chinese Han Youth.

  8. Cloning of porcine GPIHBP1 gene and its tissue expression pattern and genetic effect on adipose traits.

    Science.gov (United States)

    Xu, Huaming; Tao, Xuelian; Wei, Yingying; Chen, Jianning; Xing, Shuhua; Cen, Wangmin; Wen, Anxiang; Zhu, Li; Tang, Guoqing; Li, Mingzhou; Jiang, Anan; Jiang, Yanzhi; Li, Xuewei

    2015-02-25

    Lipoprotein lipase (LPL) is a key enzyme in lipid metabolism and is transported by glycosylphosphatidylinositol-anchored high-density lipoprotein-binding protein 1 (GPIHBP1) from the interstitial spaces to the capillary lumen. Here, we cloned a cDNA and the genomic locus of the porcine GPIHBP1 gene, and investigated its tissue expression pattern and its genetic effects on adipose traits. Porcine GPIHBP1 exhibits a four-exon/three-intron structure, including a 543bp open reading frame that encodes 180 amino acids. The porcine GPIHBP1 protein shows 49%-65% homology and shares the major conserved structural domains of GPIHBP1 proteins in other mammals. Porcine GPIHBP1 mRNA levels were high in the adipose tissue, muscle and lung, and higher mRNA levels were observed in sows compared to boars in adipose tissues of the inner and outer layers of subcutaneous fat, abdominal fat, and suet fat. The mRNA expression pattern of porcine GPIHBP1 and LPL genes was similar in most tissues except for the lung. Thirty six single nucleotide polymorphisms (SNPs) were found in the porcine GPIHBP1 gene. Association analyses showed that the g.-255G>C and g.-626T>G SNPs are associated with intramuscular fat content, and that the g.-1557T>C and g.-1948G>A SNPs are associated with back fat thickness. In conclusion, porcine GPIHBP1 mRNA is abundantly expressed in the adipose tissue, muscle and lung, and gender affects GPIHBP1 mRNA expression levels; furthermore, four GPIHBP1 SNPs are genetic factors affecting adipose traits.

  9. 脂蛋白脂酶基因多态性与冠心病关系的研究%Relationship between a novel polymorphism of lipoprotein lipase gene and coronary heart disease

    Institute of Scientific and Technical Information of China (English)

    苏智广; 张思仲; 侯一平; 张立; 廖林川; 肖翠英

    2002-01-01

    目的探讨脂蛋白脂酶基因的多态性与冠心病的相关性. 方法提取冠心病群体和正常群体的基因组DNA,借助聚合酶链反应扩增LPL基因的9个外显子及其侧翼的内含子序列,采用变性高效液相色谱技术对扩增的片段进行了筛查,并用双脱氧末端终止法对扩增的片段进行了DNA序列检测.结果在LPL 基因第5外显子发现了一未见文献报道的多态位点,即 G830→A转换,该变异导致LPL 基因第192 位的Arg(CGA)被Gln(CAA)取代.经χ2检验,由此多态产生的基因型A/A和等位基因A在对照组和冠心病组之间没有显著性差异(P>0.05).对冠心病患者组进一步采用χ 2检验,发现A/A基因型和A等位基因在合并有高甘油三酯/低高密度脂蛋白胆固醇血症的患者组和血脂正常的患者组之间存在显著性差异(P0.05). However, the frequencies of A/A genotype and A allele ( 0.653 and 0.786) in CHD patients with high plasma triglyceride/lowed plasma hi gh density lipoprotein cholesterol were higher than those (0.415 and 0.642) in CHD patients without hyperlipidemia (P<0.05). Conclusion No direct association was found between the LPL Arg192Gln substitution polymor phism and CHD, but there is a significant positive correlation between the A/A g enotype of the LPL gene and CHD associated with high triglyceride/lowed high den sity lipoprotein cholesterol. This study may provide new data for exploring the molecular mechanism of CHD.

  10. Targeted capture and resequencing of 1040 genes reveal environmentally driven functional variation in grey wolves.

    Science.gov (United States)

    Schweizer, Rena M; Robinson, Jacqueline; Harrigan, Ryan; Silva, Pedro; Galverni, Marco; Musiani, Marco; Green, Richard E; Novembre, John; Wayne, Robert K

    2016-01-01

    In an era of ever-increasing amounts of whole-genome sequence data for individuals and populations, the utility of traditional single nucleotide polymorphisms (SNPs) array-based genome scans is uncertain. We previously performed a SNP array-based genome scan to identify candidate genes under selection in six distinct grey wolf (Canis lupus) ecotypes. Using this information, we designed a targeted capture array for 1040 genes, including all exons and flanking regions, as well as 5000 1-kb nongenic neutral regions, and resequenced these regions in 107 wolves. Selection tests revealed striking patterns of variation within candidate genes relative to noncandidate regions and identified potentially functional variants related to local adaptation. We found 27% and 47% of candidate genes from the previous SNP array study had functional changes that were outliers in sweed and bayenv analyses, respectively. This result verifies the use of genomewide SNP surveys to tag genes that contain functional variants between populations. We highlight nonsynonymous variants in APOB, LIPG and USH2A that occur in functional domains of these proteins, and that demonstrate high correlation with precipitation seasonality and vegetation. We find Arctic and High Arctic wolf ecotypes have higher numbers of genes under selection, which highlight their conservation value and heightened threat due to climate change. This study demonstrates that combining genomewide genotyping arrays with large-scale resequencing and environmental data provides a powerful approach to discern candidate functional variants in natural populations. © 2015 John Wiley & Sons Ltd.

  11. Knowledge-driven multi-locus analysis reveals gene-gene interactions influencing HDL cholesterol level in two independent EMR-linked biobanks.

    Science.gov (United States)

    Turner, Stephen D; Berg, Richard L; Linneman, James G; Peissig, Peggy L; Crawford, Dana C; Denny, Joshua C; Roden, Dan M; McCarty, Catherine A; Ritchie, Marylyn D; Wilke, Russell A

    2011-05-11

    Genome-wide association studies (GWAS) are routinely being used to examine the genetic contribution to complex human traits, such as high-density lipoprotein cholesterol (HDL-C). Although HDL-C levels are highly heritable (h(2)∼0.7), the genetic determinants identified through GWAS contribute to a small fraction of the variance in this trait. Reasons for this discrepancy may include rare variants, structural variants, gene-environment (GxE) interactions, and gene-gene (GxG) interactions. Clinical practice-based biobanks now allow investigators to address these challenges by conducting GWAS in the context of comprehensive electronic medical records (EMRs). Here we apply an EMR-based phenotyping approach, within the context of routine care, to replicate several known associations between HDL-C and previously characterized genetic variants: CETP (rs3764261, p = 1.22e-25), LIPC (rs11855284, p = 3.92e-14), LPL (rs12678919, p = 1.99e-7), and the APOA1/C3/A4/A5 locus (rs964184, p = 1.06e-5), all adjusted for age, gender, body mass index (BMI), and smoking status. By using a novel approach which censors data based on relevant co-morbidities and lipid modifying medications to construct a more rigorous HDL-C phenotype, we identified an association between HDL-C and TRIB1, a gene which previously resisted identification in studies with larger sample sizes. Through the application of additional analytical strategies incorporating biological knowledge, we further identified 11 significant GxG interaction models in our discovery cohort, 8 of which show evidence of replication in a second biobank cohort. The strongest predictive model included a pairwise interaction between LPL (which modulates the incorporation of triglyceride into HDL) and ABCA1 (which modulates the incorporation of free cholesterol into HDL). These results demonstrate that gene-gene interactions modulate complex human traits, including HDL cholesterol.

  12. Response of genes involved in lipid metabolism in rat epididymal white adipose tissue to different fasting conditions after long-term fructose consumption.

    Science.gov (United States)

    Li, Jin-Xiu; Ke, Da-Zhi; Yao, Ling; Wang, Shang; Ma, Peng; Liu, Li; Zuo, Guo-Wei; Jiang, Li-Rong; Wang, Jian-Wei

    2017-03-04

    There has been much concern regarding the dietary fructose contributes to the development of metabolic syndrome. High-fructose diet changes the expression of genes involved in lipid metabolism. Levels of a number of hepatic lipogenic enzymes are increased by a high-carbohydrate diet in fasted-refed model rats/mice. Both the white adipose tissue (WAT) and the liver play a key role in the maintenance of nutrient homeostasis. Here, the aim of this study was to analyze the expression of key genes related to lipid metabolism in epididymal WAT (eWAT) in response to different fasting condition after long-term chronic fructose consumption. Rats were fed standard chow supplemented with 10% w/v fructose solution for 5 weeks, and killed after chow-fasting and fructose withdrawal (fasting) or chow-fasting and continued fructose (fructose alone) for 14 h. Blood parameters and the expression of genes involved in fatty acid synthesis (ChREBP, SREBP-1c, FAS, SCD1), triglyceride biosynthesis (DGAT-1, DGAT-2) and lipid mobilization (ATGL, HSL) in eWAT were analyzed. In addition, mRNA levels of PPAR-γ, CD36 and LPL were also detected. As expected, fructose alone increased the mRNA expression of FAS, SCD1, and correspondingly decreased ATGL and HSL mRNA levels. However, ChREBP, DGAT-2, ATGL and HSL mRNA levels restored near to normal while FAS and SCD1 tend to basic level under fasting condition. The mRNA expression of SREBP-1c, PPAR-γ and LPL did not changed at any situations but CD36 mRNA decreased remarkably in fructose alone group. In conclusion, these findings demonstrate that genes involved in lipid metabolism in rat eWAT are varied in response to different fasting conditions after long-term fructose consumption. Copyright © 2017. Published by Elsevier Inc.

  13. Brown fat like gene expression in the epicardial fat depot correlates with circulating HDL-cholesterol and triglycerides in patients with coronary artery disease.

    Science.gov (United States)

    Chechi, Kanta; Blanchard, Pierre-Gilles; Mathieu, Patrick; Deshaies, Yves; Richard, Denis

    2013-09-01

    Recent evidence indicates that epicardial adipose tissue (EAT) expresses uncoupling protein-1 (UCP1), a marker of brown adipocytes. However, the putative effects of the presence of brown adipocytes in EAT remain unknown. The mRNA expression of genes related to brown adipocyte-mediated thermogenesis was measured in the fat samples collected from the epicardial-, mediastinal- and subcutaneous-depots of patients undergoing coronary artery bypass grafting. Both univariate and multivariate analyses were then utilized to determine any association between gene expression and the anthropometrics and fasting blood chemistries of these patients. EAT exhibited significantly higher expression of UCP1 and cytochrome c oxidase subunit-IV (COX-IV) compared to mediastinal- and subcutaneous-fat depots (P ≤ 0.05). EAT expression of UCP1 (r=0.50), COX-IV (r=0.37) and lipoprotein lipase (LPL) (r=0.58) positively associated with circulating levels of HDL-cholesterol (P ≤ 0.05). In addition, EAT expression of LPL, acyl coA dehydrogenase-short, -medium and -long chain genes associated negatively with circulating TG levels (P ≤ 0.05). Abundance of UCP-1 in the EAT relative to other fat depots confirms the presence of brown adipocytes in human EAT. Furthermore, the correlations among the EAT expression of thermogenesis-related genes with the circulating HDL and TG levels indicate that presence of active brown adipocytes shares a functional association with the circulating plasma lipids in humans. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  14. Update on the molecular biology of dyslipidemias.

    Science.gov (United States)

    Ramasamy, I

    2016-02-15

    Dyslipidemia is a commonly encountered clinical condition and is an important determinant of cardiovascular disease. Although secondary factors play a role in clinical expression, dyslipidemias have a strong genetic component. Familial hypercholesterolemia is usually due to loss-of-function mutations in LDLR, the gene coding for low density lipoprotein receptor and genes encoding for proteins that interact with the receptor: APOB, PCSK9 and LDLRAP1. Monogenic hypertriglyceridemia is the result of mutations in genes that regulate the metabolism of triglyceride rich lipoproteins (eg LPL, APOC2, APOA5, LMF1, GPIHBP1). Conversely familial hypobetalipoproteinemia is caused by inactivation of the PCSK9 gene which increases the number of LDL receptors and decreases plasma cholesterol. Mutations in the genes APOB, and ANGPTL3 and ANGPTL4 (that encode angiopoietin-like proteins which inhibit lipoprotein lipase activity) can further cause low levels of apoB containing lipoproteins. Abetalipoproteinemia and chylomicron retention disease are due to mutations in the microsomal transfer protein and Sar1b-GTPase genes, which affect the secretion of apoB containing lipoproteins. Dysbetalipoproteinemia stems from dysfunctional apoE and is characterized by the accumulation of remnants of chylomicrons and very low density lipoproteins. ApoE deficiency can cause a similar phenotype or rarely mutations in apoE can be associated with lipoprotein glomerulopathy. Low HDL can result from mutations in a number of genes regulating HDL production or catabolism; apoAI, lecithin: cholesterol acyltransferase and the ATP-binding cassette transporter ABCA1. Patients with cholesteryl ester transfer protein deficiency have markedly increased HDL cholesterol. Both common and rare genetic variants contribute to susceptibility to dyslipidemias. In contrast to rare familial syndromes, in most patients, dyslipidemias have a complex genetic etiology consisting of multiple genetic variants as established

  15. Association of adipocyte genes with ASP expression: a microarray analysis of subcutaneous and omental adipose tissue in morbidly obese subjects

    Directory of Open Access Journals (Sweden)

    Lu HuiLing

    2010-01-01

    Full Text Available Abstract Background Prevalence of obesity is increasing to pandemic proportions. However, obese subjects differ in insulin resistance, adipokine production and co-morbidities. Based on fasting plasma analysis, obese subjects were grouped as Low Acylation Stimulating protein (ASP and Triglyceride (TG (LAT vs High ASP and TG (HAT. Subcutaneous (SC and omental (OM adipose tissues (n = 21 were analysed by microarray, and biologic pathways in lipid metabolism and inflammation were specifically examined. Methods LAT and HAT groups were matched in age, obesity, insulin, and glucose, and had similar expression of insulin-related genes (InsR, IRS-1. ASP related genes tended to be increased in the HAT group and were correlated (factor B, adipsin, complement C3, p Results HAT adipose tissue demonstrated increased lipid related genes for storage (CD36, DGAT1, DGAT2, SCD1, FASN, and LPL, lipolysis (HSL, CES1, perilipin, fatty acid binding proteins (FABP1, FABP3 and adipocyte differentiation markers (CEBPα, CEBPβ, PPARγ. By contrast, oxidation related genes were decreased (AMPK, UCP1, CPT1, FABP7. HAT subjects had increased anti-inflammatory genes TGFB1, TIMP1, TIMP3, and TIMP4 while proinflammatory PIG7 and MMP2 were also significantly increased; all genes, p Conclusion Taken together, the profile of C5L2 receptor, ASP gene expression and metabolic factors in adipose tissue from morbidly obese HAT subjects suggests a compensatory response associated with the increased plasma ASP and TG.

  16. Transcriptional regulation of cardiac genes balance pro- and anti-hypertrophic mechanisms in hypertrophic cardiomyopathy

    Directory of Open Access Journals (Sweden)

    Nina Gennebäck

    2012-06-01

    Full Text Available Hypertrophic cardiomyopathy (HCM is characterized by unexplained left ventricular hypertrophy. HCM is often hereditary, but our knowledge of the mechanisms leading from mutation to phenotype is incomplete. The transcriptional expression patterns in the myocar - dium of HCM patients may contribute to understanding the mechanisms that drive and stabilize the hypertrophy. Cardiac myectomies/biopsies from 8 patients with hypertrophic obstructive cardiomyopathy (HOCM and 5 controls were studied with whole genome Illumina microarray gene expression (detecting 18 189 mRNA. When comparing HOCM myocardium to controls, there was significant transcriptional down-regulation of the MYH6, EGR1, APOB and FOS genes, and significant transcriptional up-regulation of the ACE2, JAK2, NPPA (ANP, APOA1 and HDAC5 genes. The transcriptional regulation revealed both pro- and anti-hypertrophic mechanisms. The pro-hypertrophic response was explained by the transcriptional down-regulation of MYH6, indicating that the switch to the fetal gene program is maintained, and the transcriptional up-regulation of JAK2 in the JAK-STAT pathway. The anti-hypertrophic response was seen as a transcriptional down-regulation of the immediate early genes (IEGs, FOS and EGR1, and a transcriptional up-regulation of ACE2 and HDAC5. This can be interpreted as a transcriptional endogenous protection system in the heart of the HOCM patients, neither growing nor suppressing the already hypertrophic myocardium.

  17. Regulation of plasma LDL: the apoB paradigm.

    NARCIS (Netherlands)

    Sniderman, A.D.; Graaf, J. de; Couture, P.; Williams, K.; Kiss, R.S.; Watts, G.F.

    2010-01-01

    The objectives of this analysis are to re-examine the foundational studies of the in vivo metabolism of plasma LDL (low-density lipoprotein) particles in humans and, based on them, to reconstruct our understanding of the governance of the concentration of plasma LDL and the maintenance of cholestero

  18. Association of adipocyte genes with ASP expression: a microarray analysis of subcutaneous and omental adipose tissue in morbidly obese subjects

    Science.gov (United States)

    2010-01-01

    Background Prevalence of obesity is increasing to pandemic proportions. However, obese subjects differ in insulin resistance, adipokine production and co-morbidities. Based on fasting plasma analysis, obese subjects were grouped as Low Acylation Stimulating protein (ASP) and Triglyceride (TG) (LAT) vs High ASP and TG (HAT). Subcutaneous (SC) and omental (OM) adipose tissues (n = 21) were analysed by microarray, and biologic pathways in lipid metabolism and inflammation were specifically examined. Methods LAT and HAT groups were matched in age, obesity, insulin, and glucose, and had similar expression of insulin-related genes (InsR, IRS-1). ASP related genes tended to be increased in the HAT group and were correlated (factor B, adipsin, complement C3, p tissue, with little difference in OM tissue. Increased C5L2 (p tissue demonstrated increased lipid related genes for storage (CD36, DGAT1, DGAT2, SCD1, FASN, and LPL), lipolysis (HSL, CES1, perilipin), fatty acid binding proteins (FABP1, FABP3) and adipocyte differentiation markers (CEBPα, CEBPβ, PPARγ). By contrast, oxidation related genes were decreased (AMPK, UCP1, CPT1, FABP7). HAT subjects had increased anti-inflammatory genes TGFB1, TIMP1, TIMP3, and TIMP4 while proinflammatory PIG7 and MMP2 were also significantly increased; all genes, p tissue from morbidly obese HAT subjects suggests a compensatory response associated with the increased plasma ASP and TG. PMID:20105310

  19. Mutations of the microsomal triglyceride-transfer-protein gene in abetalipoproteinemia

    Energy Technology Data Exchange (ETDEWEB)

    Narcisi, T.M.E.; Shoulders, C.C.; Chester, S.A. [Hammersmith Hospital, London (United Kingdom)] [and others

    1995-12-01

    Elevated plasma levels of apolipoprotein B (apoB)-containing lipoproteins constitute a major risk factor for the development of coronary heart disease. In the rare recessively inherited disorder abetalipoproteinemia (ABL) the production of apoB-containing lipoproteins is abolished, despite no abnormality of the apoB gene. In the current study we have characterized the gene encoding a microsomal triglyceride-transfer protein (MTP), localized to chromosome 4q22-24, and have identified a mutation of the MTP gene in both alleles of all individuals in a cohort of eight patients with classical ABL. Each mutant allele is predicted to encode a truncated form of MTP with a variable number of aberrant amino acids at its C-terminal end. Expression of genetically engineered forms of MTP in Cos-1 cells indicates that the C-terminal portion of MTP is necessary for triglyceride-transfer activity. Deletion of 20 amino acids from the carboxyl terminus of the 894-amino-acid protein and a missense mutation of cysteine 878 to serine both abolished activity. These results establish that defects of the MTP gene are the predominant, if not sole, cause of hereditary ABL and that an intact carboxyl terminus is necessary for activity. 49 refs., 4 figs., 5 tabs.

  20. Pleiotropic genes for metabolic syndrome and inflammation

    Science.gov (United States)

    Kraja, Aldi T.; Chasman, Daniel I.; North, Kari E.; Reiner, Alexander P.; Yanek, Lisa R.; Kilpeläinen, Tuomas O.; Smith, Jennifer A.; Dehghan, Abbas; Dupuis, Josée; Johnson, Andrew D.; Feitosa, Mary F.; Tekola-Ayele, Fasil; Chu, Audrey Y.; Nolte, Ilja M.; Dastani, Zari; Morris, Andrew; Pendergrass, Sarah A.; Sun, Yan V.; Ritchie, Marylyn D.; Vaez, Ahmad; Lin, Honghuang; Ligthart, Symen; Marullo, Letizia; Rohde, Rebecca; Shao, Yaming; Ziegler, Mark A.; Im, Hae Kyung; Schnabel, Renate B.; Jørgensen, Torben; Jørgensen, Marit E.; Hansen, Torben; Pedersen, Oluf; Stolk, Ronald P.; Snieder, Harold; Hofman, Albert; Uitterlinden, Andre G.; Franco, Oscar H.; Ikram, M. Arfan; Richards, J. Brent; Rotimi, Charles; Wilson, James G.; Lange, Leslie; Ganesh, Santhi K.; Nalls, Mike; Rasmussen-Torvik, Laura J.; Pankow, James S.; Coresh, Josef; Tang, Weihong; Kao, W.H. Linda; Boerwinkle, Eric; Morrison, Alanna C.; Ridker, Paul M.; Becker, Diane M.; Rotter, Jerome I.; Kardia, Sharon L.R.; Loos, Ruth J.F.; Larson, Martin G.; Hsu, Yi-Hsiang; Province, Michael A.; Tracy, Russell; Voight, Benjamin F.; Vaidya, Dhananjay; O’Donnell, Christopher; Benjamin, Emelia J.; Alizadeh, Behrooz Z.; Prokopenko, Inga; Meigs, James B.; Borecki, Ingrid B.

    2014-01-01

    Metabolic syndrome (MetS) has become a health and financial burden worldwide. The MetS definition captures clustering of risk factors that predict higher risk for diabetes mellitus and cardiovascular disease. Our study hypothesis is that additional to genes influencing individual MetS risk factors, genetic variants exist that influence MetS and inflammatory markers forming a predisposing MetS genetic network. To test this hypothesis a staged approach was undertaken. (a) We analyzed 17 metabolic and inflammatory traits in more than 85,500 participants from 14 large epidemiological studies within the Cross Consortia Pleiotropy Group. Individuals classified with MetS (NCEP definition), versus those without, showed on average significantly different levels for most inflammatory markers studied. (b) Paired average correlations between 8 metabolic traits and 9 inflammatory markers from the same studies as above, estimated with two methods, and factor analyses on large simulated data, helped in identifying 8 combinations of traits for follow-up in meta-analyses, out of 130,305 possible combinations between metabolic traits and inflammatory markers studied. (c) We performed correlated meta-analyses for 8 metabolic traits and 6 inflammatory markers by using existing GWAS published genetic summary results, with about 2.5 million SNPs from twelve predominantly largest GWAS consortia. These analyses yielded 130 unique SNPs/genes with pleiotropic associations (a SNP/gene associating at least one metabolic trait and one inflammatory marker). Of them twenty-five variants (seven loci newly reported) are proposed as MetS candidates. They map to genes MACF1, KIAA0754, GCKR, GRB14, COBLL1, LOC646736-IRS1, SLC39A8, NELFE, SKIV2L, STK19, TFAP2B, BAZ1B, BCL7B, TBL2, MLXIPL, LPL, TRIB1, ATXN2, HECTD4, PTPN11, ZNF664, PDXDC1, FTO, MC4R and TOMM40. Based on large data evidence, we conclude that inflammation is a feature of MetS and several gene variants show pleiotropic genetic

  1. S447X variant of the lipoprotein lipase gene, lipids, and risk of coronary heart disease in 3 prospective cohort studies

    DEFF Research Database (Denmark)

    Jensen, M.K.; Rimm, E.B.; Rader, D.

    2009-01-01

    in this gene, we investigated the association between the LPL S447X variant with lipids and risk of coronary heart disease (CHD) in 3 independent, prospective studies. Methods The S447X variant was genotyped in case-control studies of incident CHD nested within the Nurses' Health Study (NHS), the Health......; the association was weaker in the HPFS and not statistically significant in the DCH women and men. The pooled relative risk per minor allele was 0.74 (0.56-1.00). There was a suggestion that the associations of the S447X variant with plasma lipids and CHD risk were more pronounced in obese individuals in the NHS...... whether greater benefit from this variant may be conferred in some subgroups. (Am Heart J 2009;157:384-90.)...

  2. Gene Expression Signature in Adipose Tissue of Acromegaly Patients

    Science.gov (United States)

    Hochberg, Irit; Tran, Quynh T.; Barkan, Ariel L.; Saltiel, Alan R.; Chandler, William F.; Bridges, Dave

    2015-01-01

    To study the effect of chronic excess growth hormone on adipose tissue, we performed RNA sequencing in adipose tissue biopsies from patients with acromegaly (n = 7) or non-functioning pituitary adenomas (n = 11). The patients underwent clinical and metabolic profiling including assessment of HOMA-IR. Explants of adipose tissue were assayed ex vivo for lipolysis and ceramide levels. Patients with acromegaly had higher glucose, higher insulin levels and higher HOMA-IR score. We observed several previously reported transcriptional changes (IGF1, IGFBP3, CISH, SOCS2) that are known to be induced by GH/IGF-1 in liver but are also induced in adipose tissue. We also identified several novel transcriptional changes, some of which may be important for GH/IGF responses (PTPN3 and PTPN4) and the effects of acromegaly on growth and proliferation. Several differentially expressed transcripts may be important in GH/IGF-1-induced metabolic changes. Specifically, induction of LPL, ABHD5, and NRIP1 can contribute to enhanced lipolysis and may explain the elevated adipose tissue lipolysis in acromegalic patients. Higher expression of TCF7L2 and the fatty acid desaturases FADS1, FADS2 and SCD could contribute to insulin resistance. Ceramides were not different between the two groups. In summary, we have identified the acromegaly gene expression signature in human adipose tissue. The significance of altered expression of specific transcripts will enhance our understanding of the metabolic and proliferative changes associated with acromegaly. PMID:26087292

  3. Gene Expression Signature in Adipose Tissue of Acromegaly Patients.

    Science.gov (United States)

    Hochberg, Irit; Tran, Quynh T; Barkan, Ariel L; Saltiel, Alan R; Chandler, William F; Bridges, Dave

    2015-01-01

    To study the effect of chronic excess growth hormone on adipose tissue, we performed RNA sequencing in adipose tissue biopsies from patients with acromegaly (n = 7) or non-functioning pituitary adenomas (n = 11). The patients underwent clinical and metabolic profiling including assessment of HOMA-IR. Explants of adipose tissue were assayed ex vivo for lipolysis and ceramide levels. Patients with acromegaly had higher glucose, higher insulin levels and higher HOMA-IR score. We observed several previously reported transcriptional changes (IGF1, IGFBP3, CISH, SOCS2) that are known to be induced by GH/IGF-1 in liver but are also induced in adipose tissue. We also identified several novel transcriptional changes, some of which may be important for GH/IGF responses (PTPN3 and PTPN4) and the effects of acromegaly on growth and proliferation. Several differentially expressed transcripts may be important in GH/IGF-1-induced metabolic changes. Specifically, induction of LPL, ABHD5, and NRIP1 can contribute to enhanced lipolysis and may explain the elevated adipose tissue lipolysis in acromegalic patients. Higher expression of TCF7L2 and the fatty acid desaturases FADS1, FADS2 and SCD could contribute to insulin resistance. Ceramides were not different between the two groups. In summary, we have identified the acromegaly gene expression signature in human adipose tissue. The significance of altered expression of specific transcripts will enhance our understanding of the metabolic and proliferative changes associated with acromegaly.

  4. Interactions among the glucocorticoid receptor, lipoprotein lipase and adrenergic receptor genes and abdominal fat in the Québec Family Study.

    Science.gov (United States)

    Ukkola, O; Pérusse, L; Chagnon, Y C; Després, J P; Bouchard, C

    2001-09-01

    To investigate whether interactions between glucocorticoid receptor (GRL), lipoprotein lipase (LPL) and adrenergic receptor (ADR) gene markers contribute to individual differences in indicators of adiposity and abdominal obesity, including visceral fat level. Cross-sectional study; 742 individuals from the phase 2 of the Québec Family Study cohort. Total body fat assessed by hydrodensitometry and the sum of six skinfolds. Abdominal fat areas measured by computed tomography and adjusted for age, sex and total fat mass in all analyses. GRL Bcl I, alpha 2A-ADR Dra I and beta 2-ADR Ban I markers were typed by Southern blot, and other markers by polymerase chain reaction technique. It is confirmed that the 4.5 kb allele of the GRL BclI polymorphism is associated with a higher amount of abdominal visceral fat (AVF) depot (P for trend<0.001) independent of the level of total body fat. Furthermore, the alpha 2-ADR Dra I variant is associated with lower cross-sectional areas of abdominal total (P=0.003) and subcutaneous (P=0.012) adipose tissue. Gene-gene interactions between GRL and alpha 2-ADR genes affecting overall adiposity (P=0.016) as well as between GRL and beta 2-ADR genes (P=0.049) having influence on total abdominal fat levels were observed. When the three genes were considered together in the same analysis, significant interactions having influence on overall adiposity (P=0.017), abdominal total (P=0.032) and visceral fat (P=0.002) were observed. About 1-2% of the total variation in total fatness and abdominal fat was explained by these gene-gene interactions. There is an association between the GRL BclI polymorphism and increased AVF levels independent of the level of total body fat. The alpha 2-ADR DraI variant is associated with a lower cross-sectional area of abdominal total fat. Numerous interactions between GRL and ADR markers on overall adiposity and total abdominal fat as well as between GRL, LPL and ADR genes on overall adiposity, abdominal total and

  5. Effects of Addition of Linseed and Marine Algae to the Diet on Adipose Tissue Development, Fatty Acid Profile, Lipogenic Gene Expression, and Meat Quality in Lambs.

    Science.gov (United States)

    Urrutia, Olaia; Mendizabal, José Antonio; Insausti, Kizkitza; Soret, Beatriz; Purroy, Antonio; Arana, Ana

    2016-01-01

    This study examined the effect of linseed and algae on growth and carcass parameters, adipocyte cellularity, fatty acid profile and meat quality and gene expression in subcutaneous and intramuscular adipose tissues (AT) in lambs. After weaning, 33 lambs were fed three diets up to 26.7 ± 0.3 kg: Control diet (barley and soybean); L diet (barley, soybean and 10% linseed) and L-A diet (barley, soybean, 5% linseed and 3.89% algae). Lambs fed L-A diet showed lower average daily gain and greater slaughter age compared to Control and L (P algae increased α-linolenic acid and eicosapentaenoic acid contents in both AT (P Algae had adverse effects on meat quality, with greater lipid oxidation and reduced ratings for odor and flavor. The expression of lipogenic genes was downregulated in the subcutaneous AT (P < 0.05): acetyl-CoA carboxylase 1 (ACACA) in L and L-A and lipoprotein lipase (LPL) and stearoyl-CoA desaturase (SCD) in L-A. Fatty acid desaturase 1 (FADS1), fatty acid desaturase 2 (FADS2) and fatty acid elongase 5 (ELOVL5) were unaffected. In the subcutaneous AT, supplementing either L or L-A increased peroxisome proliferator-activated receptor gamma (PPARG) and CAAT-enhancer binding protein alpha (CEBPA) (P < 0.05), although it had no effect on sterol regulatory element-binding factor 1 (SREBF1). In the intramuscular AT, expression of ACACA, SCD, FADS1 and FADS2 decreased in L and L-A (P < 0.001) and LPL in L (P < 0.01), but PPARG, CEBPA and SREBF1 were unaffected.

  6. The effect of polymorphisms in candidate genes on the long-term risk of lipodystrophy and dyslipidemia in HIV-infected white patients starting antiretroviral therapy.

    Science.gov (United States)

    Marzocchetti, Angela; Schwarz, Jessica; Di Giambenedetto, Simona; Colafigli, Manuela; Bracciale, Laura; Fabbiani, Massimilliano; Fantoni, Massimo; Trecarichi, Enrico; Cauda, Roberto; De Luca, Andrea

    2011-12-01

    We investigated whether polymorphisms in human candidate genes could be associated with a different risk of developing lipodystrophy and dyslipidemia in HIV-infected patients starting combination antiretroviral therapy (cART). Genomic DNA samples from white HIV-1-infected patients were analyzed for seven polymorphisms located in the MDR1, TNF-α, APM1, APOE, and LPL genes. Lipid data were retrospectively collected beginning with the initiation of cART. Lipodystrophy was assessed cross-sectionally and then prospectively. The association with lipodystrophy and National Cholesterol Evaluation Program Adult Treatment Panel III-defined lipid thresholds was analyzed using survival analysis and logistic regression. One-hundred and seventy-four patients were genotyped. In 151 patients assessed for lipodystrophy, MDR1 3435 T homozygosis was associated with a higher hazard (adjusted hazard ratio, aHR, versus CT 0.25; p=0.02) and tumor necrosis factor (TNF)-α 308 G homozygosis with a lower hazard (vs. AA aHR 2.14; p=0.04) of developing trunk fat accumulation after adjusting for gender and initial cART type. The TNF 238 GG genotype was associated with a higher risk of developing low HDL-cholesterol levels (adjusted odd ratio, aOR, 5.91; p=0.01) while patients carrying the LPL S477X mutation were at lower risk of reaching high non-HDL-cholesterol levels (aOR 0.39; p=0.05). The APOEe3/3 genotype patients were at lower risk (aOR 0.26, p=0.015), whereas the adiponectin 276 GT carriers were at higher risk of developing hypertriglyceremia (vs. GG aOR 3.10; p=0.04). Knowledge of the effect of genetic determinants on dyslipidemia and lipodystrophy may prompt the investigation of potential pathogenetic mechanisms and might eventually be used for guiding individualized treatment decisions.

  7. Superparamagnetic iron oxide nanoparticles alter expression of obesity and T2D-associated risk genes in human adipocytes

    Science.gov (United States)

    Sharifi, S.; Daghighi, S.; Motazacker, M. M.; Badlou, B.; Sanjabi, B.; Akbarkhanzadeh, A.; Rowshani, A. T.; Laurent, S.; Peppelenbosch, M. P.; Rezaee, F.

    2013-07-01

    Adipocytes hypertrophy is the main cause of obesity and its affliction such as type 2 diabetes (T2D). Since superparamagnetic iron oxide nanoparticles (SPIONs) are used for a wide range of biomedical/medical applications, we aimed to study the effect of SPIONs on 22 and 29 risk genes (Based on gene wide association studies) for obesity and T2D in human adipocytes. The mRNA expression of lipid and glucose metabolism genes was changed upon the treatment of human primary adipocytes with SPIONs. mRNA of GULP1, SLC30A8, NEGR1, SEC16B, MTCH2, MAF, MC4R, and TMEM195 were severely induced, whereas INSIG2, NAMPT, MTMR9, PFKP, KCTD15, LPL and GNPDA2 were down-regulated upon SPIONs stimulation. Since SEC16B gene assist the phagocytosis of apoptotic cells and this gene were highly expressed upon SPIONs treatment in adipocytes, it is logic to assume that SPIONs may play a crucial role in this direction, which requires more consideration in the future.

  8. Effects of CpG-ODN on gene expression in formation of foam cells

    Institute of Scientific and Technical Information of China (English)

    Kai LI; Bin WAN; Zhen-lin HU; Ying HE; Xiao-wen HE; Lei JIANG; Shu-han SUN

    2005-01-01

    Aim: To investigate the effects of CpG-oligodeoxynucleotide (CpG-ODN) on the formation of macrophage foam cells and related gene expression. Methods: A gene expression profile was examined by microarray techniques, and mRNA expression was detected by reverse transcriptase polymerase chain reaction (RTPCR). The cholesterol and cholesteryl ester contents of cells were determined by high performance liquid chromatography. Results: CD36, LPL, and Fcγ2b, which were related to lipid metabolism and the formation of macrophage foam cells, were upregulated after CpG-ODN stimulation. The mRNA expression related to the formation of foam cells was confirmed by semiquantitative RT-PCR. Moreover,histochemical analysis confirmed that lipid deposits inside cells increased after CpG-ODN treatment. However, using flow cytometry, we found that CpG-ODN had no effect on the expression of membrane receptors. Conclusion: CpG-ODN up-regulated the expression of genes in macrophage foam cell formation.

  9. Two novel rare variants of APOA5 gene found in subjects with severe hypertriglyceridemia.

    Science.gov (United States)

    Pisciotta, Livia; Fresa, Raffaele; Bellocchio, Antonella; Guido, Virgilia; Priore Oliva, Claudio; Calandra, Sebastiano; Bertolini, Stefano

    2011-11-20

    Common variants of APOA5 gene affect plasma triglyceride (TG) in the population and a number of rare variants APOA5 have been reported in individuals with hypertriglyceridemia (HTG). APOA5 was analysed in 98 HTG individuals (plasma TG >9 mmol/L) in whom no mutations in LPL and APOC2 had been found. Two patients were found to be heterozygous for two novel APOA5 variants. The first variant (p.L253P) was identified in an obese male who consumed a diet rich in fat and simple sugars. He was also a carrier in trans of the common TG-raising p.S19W SNP (5*3 haplotype). The second variant (c.295-297 del GAG, p.E99 del) was found in a lean male with no life style or metabolic factors known to affect plasma TG. He was a carrier in trans of the TG-raising 5*2 haplotype and was homozygous for the rare c.1337T allele of a SNP of GCKR gene. No mutations in other genes affecting plasma TG (LMF1 and GPIHBP1) were found in these patients. These APOA5 variants, resulted to be deleterious in silico, were not found in 350 control subjects. These novel APOA5 variants predispose to HTG in combination with other genetic or nutritional factors. Copyright © 2011 Elsevier B.V. All rights reserved.

  10. Regulation of the clock gene expression in human adipose tissue by weight loss.

    Science.gov (United States)

    Pivovarova, O; Gögebakan, Ö; Sucher, S; Groth, J; Murahovschi, V; Kessler, K; Osterhoff, M; Rudovich, N; Kramer, A; Pfeiffer, A F H

    2016-06-01

    The circadian clock coordinates numerous metabolic processes to adapt physiological responses to light-dark and feeding regimens and is itself regulated by metabolic cues. The implication of the circadian clock in the regulation of energy balance and body weight is widely studied in rodents but not in humans. Here we investigated (1) whether the expression of clock genes in human adipose tissue is changed by weight loss and (2) whether these alterations are associated with metabolic parameters. Subcutaneous adipose tissue (SAT) samples were collected before and after 8 weeks of weight loss on an 800 kcal per day hypocaloric diet (plus 200 g per day vegetables) at the same time of the day. Fifty overweight subjects who lost at least 8% weight after 8 weeks were selected for the study. The expression of 10 clock genes and key metabolic and inflammatory genes in adipose tissue was determined by quantitative real-time PCR. The expression of core clock genes PER2 and NR1D1 was increased after the weight loss. Correlations of PERIOD expression with body mass index (BMI) and serum total, high-density lipoprotein and low-density lipoprotein (LDL) cholesterol levels and of NR1D1 expression with total and LDL cholesterol were found that became non-significant after correction for multiple testing. Clock gene expression levels and their weight loss-induced changes tightly correlated with each other and with genes involved in fat metabolism (FASN, CPT1A, LPL, PPARG, PGC1A, ADIPOQ), energy metabolism (SIRT1), autophagy (LC3A, LC3B) and inflammatory response (NFKB1, NFKBIA, NLRP3, EMR1). Clock gene expression in human SAT is regulated by body weight changes and associated with BMI, serum cholesterol levels and the expression of metabolic and inflammatory genes. Our data confirm the tight crosstalk between molecular clock and metabolic and inflammatory pathways involved in adapting adipose tissue metabolism to changes of the energy intake in humans.

  11. Familial hypercholesterolemia in St-Petersburg: the known and novel mutations found in the low density lipoprotein receptor gene in Russia.

    Science.gov (United States)

    Zakharova, Faina M; Damgaard, Dorte; Mandelshtam, Michail Y; Golubkov, Valery I; Nissen, Peter H; Nilsen, Gitte G; Stenderup, Anette; Lipovetsky, Boris M; Konstantinov, Vladimir O; Denisenko, Alexander D; Vasilyev, Vadim B; Faergeman, Ole

    2005-02-08

    Familial hypercholesterolemia is a human monogenic disease caused by population-specific mutations in the low density lipoprotein (LDL) receptor gene. Despite thirteen different mutations of the LDL receptor gene were reported from Russia prior to 2003, the whole spectrum of disease-causing gene alterations in this country is poorly known and requires further investigation provided by the current study. Forty-five patients with clinical diagnosis of FH were tested for the apolipoprotein B (apoB) mutation R3500Q by restriction fragment length analysis. After exclusion of R3500Q mutation high-sensitive fluorescent single-strand conformation polymorphism (SSCP) analysis and automatic DNA sequencing were used to search for mutations in the LDL receptor gene. We found twenty one rare sequence variations of the LDL receptor gene. Nineteen were probably pathogenic mutations, and two (P518P, T705I) were considered as neutral ones. Among the mutations likely to be pathogenic, eight were novel (c.670-671insG, C249X, c.936-940del5, c.1291-1331del41, W422X, c.1855-1856insA, D601N, C646S), and eleven (Q12X, IVS3+1G>A, c.651-653del3, E207X, c.925-931del7, C308Y, L380H, c.1302delG, IVS9+1G>A, V776M, V806I) have already been described in other populations. None of the patients had the R3500Q mutation in the apoB gene. Nineteen pathogenic mutations in the LDL receptor gene in 23 probands were identified. Two mutations c.925-931del7 and L380H are shared by St.-Petersburg population with neighbouring Finland and several other mutations with Norway, Sweden or Denmark, i.e. countries from the Baltic Sea region. Only four mutations (c.313+1G>A, c.651-653del3, C308Y and W422X) were recurrent as all those were found in two unrelated families. By this study the number of known mutations in the LDL receptor gene in St.-Petersburg area was increased nearly threefold. Analysis of all 34 low density lipoprotein receptor gene mutations found in St.-Petersburg argues against strong founder

  12. Familial hypercholesterolemia in St.-Petersburg: the known and novel mutations found in the low density lipoprotein receptor gene in Russia

    Directory of Open Access Journals (Sweden)

    Konstantinov Vladimir O

    2005-02-01

    Full Text Available Abstract Background Familial hypercholesterolemia is a human monogenic disease caused by population-specific mutations in the low density lipoprotein (LDL receptor gene. Despite thirteen different mutations of the LDL receptor gene were reported from Russia prior to 2003, the whole spectrum of disease-causing gene alterations in this country is poorly known and requires further investigation provided by the current study. Methods Forty-five patients with clinical diagnosis of FH were tested for the apolipoprotein B (apoB mutation R3500Q by restriction fragment length analysis. After exclusion of R3500Q mutation high-sensitive fluorescent single-strand conformation polymorphism (SSCP analysis and automatic DNA sequencing were used to search for mutations in the LDL receptor gene. Results We found twenty one rare sequence variations of the LDL receptor gene. Nineteen were probably pathogenic mutations, and two (P518P, T705I were considered as neutral ones. Among the mutations likely to be pathogenic, eight were novel (c.670-671insG, C249X, c.936-940del5, c.1291-1331del41, W422X, c.1855-1856insA, D601N, C646S, and eleven (Q12X, IVS3+1G>A, c.651-653del3, E207X, c.925-931del7, C308Y, L380H, c.1302delG, IVS9+1G>A, V776M, V806I have already been described in other populations. None of the patients had the R3500Q mutation in the apoB gene. Conclusions Nineteen pathogenic mutations in the LDL receptor gene in 23 probands were identified. Two mutations c.925-931del7 and L380H are shared by St.-Petersburg population with neighbouring Finland and several other mutations with Norway, Sweden or Denmark, i.e. countries from the Baltic Sea region. Only four mutations (c.313+1G>A, c.651-653del3, C308Y and W422X were recurrent as all those were found in two unrelated families. By this study the number of known mutations in the LDL receptor gene in St.-Petersburg area was increased nearly threefold. Analysis of all 34 low density lipoprotein receptor gene

  13. Studying Genes

    Science.gov (United States)

    ... NIGMS NIGMS Home > Science Education > Studying Genes Studying Genes Tagline (Optional) Middle/Main Content Area Other Fact Sheets What are genes? Genes are segments of DNA that contain instructions ...

  14. 蚯蚓冻干粉对高血脂症小鼠载脂蛋白AI和载脂蛋白B基因表达的影响%Effects of earthworm lyophilized powder on ApoAI and ApoB gene expression in hyperlipidemic mice

    Institute of Scientific and Technical Information of China (English)

    武金霞; 田志鹏; 单彪; 甄兴航; 张贺迎

    2010-01-01

    目的 研究蚯蚓冻干粉(earthworm lyophilized powder,ELP)的降血脂作用是否与调节载脂蛋白AI(apolipoprotein AI,ApoAI)和载脂蛋白B(apolipoprotein B,ApoB)基因表达有关.方法 健康昆明种小鼠60只,随机分为5组,基础饲料组(normal diet control group,NCG)、高脂饲料组(high fat diet control group,HCG)、高脂饲料+高剂量ELP组(high-dose gavage group,HDG)、高脂饲料+中剂量ELP组(middle-dose gavage group,MDG)、高脂饲料+低剂量ELP组(low-dose gavage group,LDG).ELP干预10周后,测定各组小鼠血脂水平,RT-PCR测定各组小鼠肝脏ApoAI、ApoB mRNA表达量.结果 ELP明显降低高血脂小鼠血浆TG(total cholesterol)、TG(triglycerol)和LDL-C(low-density lipoprotein-cholesterol)水平,同时升高HDL-C(high-density lipoprotein-cholesterol)水平.HDG组和MDG组小鼠ApoAI mRNA表达量明显上升,ApoB mRNA表达量明显降低.结论 ELP具有明显的降血脂作用,其降血脂作用可能与其调节载脂蛋白基因表达有关.

  15. Maternal undernutrition alters fat cell size distribution, but not lipogenic gene expression, in the visceral fat of the late gestation guinea pig fetus.

    Science.gov (United States)

    Nguyen, L T; Muhlhausler, B S; Botting, K J; Morrison, J L

    2010-10-01

    This study investigated the development of adipose tissue in the guinea pig and the impact of maternal undernutrition on the structural and functional characteristics of perirenal adipose tissue in the dam and fetus. Date-mated guinea pigs were provided with either ad libitum feed (Control, C) or 85% of food intake per body weight of the Controls (Undernutrition, UN). Maternal (C, n = 6; UN, n = 7) perirenal adipose tissue (PAT) was collected at 60 d gestation and fetal PAT was collected at 50 d (C, n = 4) and 60 d (C, n = 8 and UN, n = 7) gestation (term, 69 d). The expression of stearoyl-CoA desaturase (SCD-1), fatty acid synthase (FAS), lipoprotein lipase (LPL), leptin and glycerol 3 phosphate dehydrogenase (G3PDH) mRNA and glucose transporters 1 and 4 (GLUT1 and GLUT4) was determined by Real Time PCR. There was no effect of maternal UN on total or relative PAT mass in the pregnant dam. There was an increase in G3PDH, but not LPL, leptin, FAS or GLUT4 mRNA expression, in UN dams compared to Controls (P PAT mass, however, the UN fetuses had a higher percentage of larger lipid locules in their PAT compared to Controls (P PAT was not different between the Control and UN fetuses. These results support previous studies which have demonstrated that maternal undernutrition is associated with an increased accumulation of visceral adipose tissue in utero, and extend them by showing that maternal undernutrition results in early changes in the size distribution of lipid locules in visceral fat depots that precede changes in lipogenic gene expression.

  16. Immunoglobulin genes

    Energy Technology Data Exchange (ETDEWEB)

    Honjo, T. (Kyoto Univ. (Japan)); Alt, F.W. (Columbia Univ., Dobbs Ferry, NY (USA). Hudson Labs.); Rabbitts, T.H. (Medical Research Council, Cambridge (UK))

    1989-01-01

    This book reports on the structure, function, and expression of the genes encoding antibodies in normal and neoplastic cells. Topics covered are: B Cells; Organization and rearrangement of immunoglobin genes; Immunoglobin genes in disease; Immunoglobin gene expression; and Immunoglobin-related genes.

  17. Repression of glucocorticoid-stimulated angiopoietin-like 4 gene transcription by insulin.

    Science.gov (United States)

    Kuo, Taiyi; Chen, Tzu-Chieh; Yan, Stephanie; Foo, Fritz; Ching, Cecilia; McQueen, Allison; Wang, Jen-Chywan

    2014-05-01

    Angiopoietin-like 4 (Angptl4) is a glucocorticoid receptor (GR) primary target gene in hepatocytes and adipocytes. It encodes a secreted protein that inhibits extracellular LPL and promotes adipocyte lipolysis. In Angptl4 null mice, glucocorticoid-induced adipocyte lipolysis and hepatic steatosis are compromised. Markedly, insulin suppressed glucocorticoid-induced Angptl4 transcription. To unravel the mechanism, we utilized small molecules to inhibit insulin signaling components and found that phosphatidylinositol 3-kinase and Akt were vital for the suppression in H4IIE cells. A forkhead box transcription factor response element (FRE) was found near the 15 bp Angptl4 glucocorticoid response element (GRE). Mutating the Angptl4 FRE significantly reduced glucocorticoid-induced reporter gene expression in cells. Moreover, chromatin immunoprecipitation revealed that GR and FoxO1 were recruited to Angptl4 GRE and FRE in a glucocorticoid-dependent manner, and cotreatment with insulin abolished both recruitments. Furthermore, in 24 h fasted mice, significant occupancy of GR and FoxO1 at the Angptl4 GRE and FRE was found in the liver. In contrast, both occupancies were diminished after 24 h refeeding. Finally, overexpression of dominant negative FoxO1 mutant abolished glucocorticoid-induced Angptl4 expression, mimicking the insulin suppression. Overall, we demonstrate that both GR and FoxO1 are required for Angptl4 transcription activation, and that FoxO1 negatively mediates the suppressive effect of insulin.

  18. Lipoprotein Lipase and PPAR Alpha Gene Polymorphisms, Increased Very-Low-Density Lipoprotein Levels, and Decreased High-Density Lipoprotein Levels as Risk Markers for the Development of Visceral Leishmaniasis by Leishmania infantum

    Directory of Open Access Journals (Sweden)

    Márcia Dias Teixeira Carvalho

    2014-01-01

    Full Text Available In visceral leishmaniasis (VL endemic areas, a minority of infected individuals progress to disease since most of them develop protective immunity. Therefore, we investigated the risk markers of VL within nonimmune sector. Analyzing infected symptomatic and, asymptomatic, and noninfected individuals, VL patients presented with reduced high-density lipoprotein cholesterol (HDL-C, elevated triacylglycerol (TAG, and elevated very-low-density lipoprotein cholesterol (VLDL-C levels. A polymorphism analysis of the lipoprotein lipase (LPL gene using HindIII restriction digestion (N = 156 samples (H+ = the presence and H− = the absence of mutation revealed an increased adjusted odds ratio (OR of VL versus noninfected individuals when the H+/H+ was compared with the H−/H− genotype (OR = 21.3; 95% CI = 2.32–3335.3; P = 0.003. The H+/H+ genotype and the H+ allele were associated with elevated VLDL-C and TAG levels (P < 0.05 and reduced HDL-C levels (P < 0.05. An analysis of the L162V polymorphism in the peroxisome proliferator-activated receptor alpha (PPARα gene (n = 248 revealed an increased adjusted OR when the Leu/Val was compared with the Leu/Leu genotype (OR = 8.77; 95% CI = 1.41–78.70; P = 0.014. High TAG (P = 0.021 and VLDL-C (P = 0.023 levels were associated with susceptibility to VL, whereas low HDL (P = 0.006 levels with resistance to infection. The mutated LPL and the PPARα Leu/Val genotypes may be considered risk markers for the development of VL.

  19. 维吾尔族妇女宫颈癌与新一类肿瘤特异性上调表达基因调控的关系研究%The association of cervical cancer of Uyghur women with the regulation of novel tumor-specific upregulated genes

    Institute of Scientific and Technical Information of China (English)

    吐尔逊帕夏·吾布力卡斯木; 玛依拉·卡米力江; 刘开江; 希尔扎提·苏来曼; 热孜万古丽·约麦尔; 哈丽丹·热依木; Abulizi Abudula

    2014-01-01

    目的:通过新的维吾尔族妇女宫颈癌组织特异性上调表达基因的分析,探讨宫颈癌发生与基因表达调控的关系及临床意义。方法选择6种新发现的宫颈癌组织特异性上调表达候选基因,设计 mRNA 特异性引物,对25例宫颈鳞癌(cervical squamous cell carcinoma,CSCC)、22例宫颈内上皮瘤变(cervical intraepithelial neo-plasia,CIN)Ⅱ~Ⅲ和25例宫颈炎组织 RNA 进行半定量 RT-PCR 鉴定。结果 CSCC 与宫颈炎组织比较, SHISA2、SIX1、果蝇同源盒基因(DTL)、桥粒芯糖蛋白-2(DSG2)、NUP62CL 和胞嘧啶脱氨酶(APOBE63B)6种基因的 mRNA 水平均有差异(P <0.05);CSCC 与 CINⅡ~Ⅲ比较,SHISA2、SIX1、APOBEC3B 和 DSG24种基因的mRNA 水平有差异(P <0.05),而 CINⅡ~Ⅲ与宫颈炎比较,只有 SHISA2基因的 mRNA 水平差异有统计学意义(P <0.05)。结论SHISA2、SIX1、DTL、DSG2、NUP62CL 和 APOBE63B 6种基因的转录表达水平变化可能成为维吾尔族妇女宫颈癌发生的早期预警标志物。%Objective To screen novel genes upregulated in cervical cancer,and investigate association of cervical carcinogenesis with the regulation of gene expression and clinical outcome.Methods We selected six newly identified genes specific to,and upregulated in,tissue specimens of cervical carcinoma.After de-signing of mRNA sequence specific primers,the expression level of these genes was detected by semi-quantitative RT-PCR,in a total of 72 cases of fresh tissue specimens from Uyghur women with cervix le-sions including 25 cases of cervical squamous cell carcinoma (CSCC),22 cases of cervical intraepithelial ne-oplasia (CIN)and 25 cases of cervicitis or normal cervix (NC);Results The transcription levels of SHISA2,SIX1,DTL,DSG2,NUP62CL and APOBE63B were significantly different in CSCC from NC (P 0.05).Conclusion The aberrant up-regulation of SHISA2,SIX1,DTL,DSG2,NUP62CL and APOBE63B gene

  20. Endothelial and lipoprotein lipases in human and mouse placenta

    DEFF Research Database (Denmark)

    Lindegaard, Marie L S; Olivecrona, Gunilla; Christoffersen, Christina;

    2005-01-01

    Placenta expresses various lipase activities. However, a detailed characterization of the involved genes and proteins is lacking. In this study, we compared the expression of endothelial lipase (EL) and LPL in human term placenta. When placental protein extracts were separated by heparin......-Sepharose affinity chromatography, the EL protein eluted as a single peak without detectable phospholipid or triglyceride (TG) lipase activity. The major portion of LPL protein eluted slightly after EL. This peak also had no lipase activity and most likely contained monomeric LPL. Fractions eluting at a higher Na......Cl concentration contained small amounts of LPL protein (most likely dimeric LPL) and had substantial TG lipase activity. In situ hybridization studies showed EL mRNA expression in syncytiotrophoblasts and endothelial cells and LPL mRNA in syncytiotrophoblasts. In contrast, immunohistochemistry showed EL and LPL...

  1. Development of diffuse large B-cell lymphoma in a patient with Waldenström’s macroglobulinemia/ lymphoplasmacytic lymphoma: clonal identity between two B-cell neoplasms

    Directory of Open Access Journals (Sweden)

    Masayuki Shiseki

    2011-08-01

    Full Text Available Waldenström’s macroglobulinemia (WM/ lymphoplasmacytic lymphoma (LPL is an indolent mature B-cell neoplasm. In rare cases of WM/LPL, diffuse large B-cell lymphoma (DLBCL develops as a result of histologic transformation. In this report, we present a case of DLBCL developing in a patient with WM/LPL. Combination chemotherapy for DLBCL was effective and complete remission was eventually achieved. We attempted to determine the clonal relatedness between WM/LPL and DLBCL in the patient by analyzing complementarity-determining region 3 (CDR3 in the immunoglobulin heavy chain gene. A common CDR3 sequence was found in tumor cells of DLBCL and those of WM/LPL, indicating that tumor cells of DLBCL are clonally identical to those of WM/LPL. Therefore, in the present case, DLBCL is developed from WM/LPL cells by clonal evolution.

  2. The impact of the leucine 7 to proline 7 polymorphism of the neuropeptide Y gene on postprandial lipemia and on the response of serum total and lipoprotein lipids to a reduced fat diet.

    Science.gov (United States)

    Schwab, U S; Agren, J J; Valve, R; Hallikainen, M A; Sarkkinen, E S; Jauhiainen, M; Karvonen, M K; Pesonen, U; Koulu, M; Uusitupa, M I J; Savolainen, M J

    2002-02-01

    The aim of the study was to examine the impact of the leucine7 to proline7 (Leu7Pro) polymorphism of the NPY gene on postprandial (PP) lipemia, post-heparin plasma lipoprotein lipase (LPL) and hepatic lipase (HL) activities, and the response of serum lipids to a reduced fat diet. Seven middle-aged obese subjects with Leu7Pro genotype were matched with seven subjects with Leu7Leu genotype for gender, age, apolipoprotein E phenotype and BMI. These 14 subjects participated in the oral 8 h fat tolerance test. Sixty-eight slightly obese middle-aged subjects (10 with the Leu7Pro genotype) had participated in intervention studies and consumed a reduced fat diet for 8 weeks. There were no statistically significant differences in PP areas under the curve of plasma total triglycerides (TG), chylomicron TG, VLDL-TG or insulin between the genotype groups. The TG-to-cholesterol (C) ratio in VLDL was significantly lower in the subjects with Leu7Pro genotype compared to those with the Leu7Leu genotype at time points 30 min and 1 h in the fat tolerance test. Heparin-induced activities of LPL or HL or the response of serum total or LDL-C to the reduced fat diet did not differ between the groups. The NPY genotype neither affects the magnitude of postprandial lipemia induced by a fat tolerance test nor the response of serum total lipids or lipids in different lipoprotein classes to the reduced fat diet. However, this preliminary study suggests that there might be compositional differences in the lipoprotein particles between the genotype groups that affect postprandial lipid metabolism. The Council for Health Sciences of the Academy of Finland, Kuopio University Hospital and the National Technology Agency, Finland.

  3. [Identification of variants in LMF1 gene associated with primary hypertriglyceridemia].

    Science.gov (United States)

    Lamiquiz-Moneo, Itziar; Bea, Ana M; Mateo-Gallego, Rocío; Baila-Rueda, Lucía; Cenarro, Ana; Pocoví, Miguel; Civeira, Fernando; de Castro-Orós, Isabel

    2015-01-01

    The majority of severe primary hypertriglyceridemia (HTG) are diagnosed in adults, and their molecular bases have not yet been fully defined. The promoter, coding regions and intron-exon boundaries of LMF1 were sequenced in 112 patients with severe primary hipertrigliceridemia (defined as TG above 500mg/dl). Five patients (4.46%) were carriers of four rare variants in the LMF1 gene associated with HTG, which participate in lipoprotein lipase (LpL) function. Also, we have identified two common variants, c.194-28 T>G and c.729+18C>G that were associated with HTG, with a different allelic frequency to that observed in the general population. A bioinformatic analysis of all found variants was conducted, defining the following as potentially harmful: p.Arg364Gln, p.Arg451Trp, p.Pro562Arg and p.Leu85Leu. Our results suggest that LMF1 mutations are involved in a substantial proportion of cases with severe HTG, putting together the moderate-aggressive effect of rare mutations with polymorphisms classically associated with this disease.

  4. Dietary conjugated linoleic acid modify gene expression in liver, muscles, and fat tissues of finishing pigs.

    Science.gov (United States)

    Tous, N; Theil, P K; Lauridsen, C; Lizardo, R; Vilà, B; Esteve-Garcia, E

    2012-12-01

    The aim of this study was to investigate underlying mechanisms of dietary conjugated linoleic acid (CLA) on lipid metabolism in various tissues of pigs. Sixteen gilts (73 ± 3 kg) were fed a control (containing sunflower oil) or an experimental diet in which 4% of sunflower oil was replaced by CLA, and slaughtered at an average BW of 117 ± 4.9 kg. Transcription of peroxisome proliferator-activated receptor alpha (PPARα), peroxisome proliferator-activated receptor gamma (PPARγ), fatty acid synthase (FAS), sterol regulatory element binding protein (SREBP1), acetyl-CoA carboxylase (ACC), lipoprotein lipase (LPL), delta-6-desaturase (D6D), and stearoyl CoA desaturase (SCD) were determined by real-time PCR in longissimus thoracis (LT) and semimembranosus (SM) muscles, LT subcutaneous and SM intermuscular fat, and in the liver. Fatty acid (FA) composition was analyzed using gas chromatography in these tissues, except for SM intermuscular fat. Dietary CLA increased PPARγ in LT muscle (P tissues studied (P muscle and liver (SREBP1, both P muscle and reduced (P muscle and intermuscular fat. Saturated FA were increased in all studied tissues (P tissue-specific way by CLA. It was concluded that dietary CLA affected transcription of genes and fat metabolism in a tissue-specific manner.

  5. Diagnosis of mantle cell lymphoma and detection of bcl-1 gene rearrangement

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Seung Sook; Cho, Kyung Ja; Lee, Sun Joo [Korea Cancer Center Hospital, Seoul (Korea, Republic of)

    1996-12-01

    We reclassified a large series of non-Hogkin`s lymphoma diagnosed at Korea Cancer Center Hospital from 1991 to 1995, according to REAL classification, and compared the efficacy of immunohistochemical study for cyclin D1 protein and PCR for bcl-1 gene rearrangement to diagnose mantle cell lymphoma (MCL). By REAL classification, 7 %, diffuse large B-cell lymphoma was the most common type (51.8%) and was followed by peripheral T-cell lymphoma-unspecified (10%) and angiocentric lymphoma (7.5%). The most reliable histologic finding was mitosis to make a differential diagnosis. Mitoses of MCL were 17/10 HPF in average and all the cases showed more than 10/10 HPF. Immunophenotypic study alone cannot lead to a differential diagnosis between MCL and SLL, and the overexpression of cyclin D1 was the most important for diagnosis of MCL . Both immunohistochemistry for cyclin D1 and PCR for bcl-1 were specific for MCL and immunohistochemistry was more sensitive than PCR. Statistical analysis showed a different survival rate between MCL and the other low-grade B-cell lymphomas (SLL + MALT + LPL) and a difference between MCL and SLL. Immunohistochemical detection of cyclin D1 has a practical usefulness in making routine diagnosis of MCL. The initial accurate diagnosis of MCL will help clinicians make a proper management. (author). 27 refs., 6 tabs., 4 figs.

  6. Identification of rice blast fungal elicitor-responsive genes by differential display analysis.

    Science.gov (United States)

    Kim, C Y; Lee, S H; Park, H C; Bae, C G; Cheong, Y H; Choi, Y J; Han, C; Lee, S Y; Lim, C O; Cho, M J

    2000-04-01

    In order to study molecular interactions that occur between rice and rice blast fungus upon infection, we isolated fungal elicitor-responsive genes from rice (Oryza sativa cv. Milyang 117) suspension-cultured cells treated with fungal elicitor prepared from the rice blast fungus (Magnaporthe grisea) employing a method that combined mRNA differential display and cDNA library screening. Data base searches with the isolated cDNA clones revealed that the OsERG1 and OsERG2 cDNAs share significant similarities with the mammalian Ca2+-dependent lipid binding (C2) domains. The OsCPX1 cDNA is highly homologous to peroxidases. The OsHin1 cDNA exhibits homology to the tobacco hin1 gene, whose expression is induced by avirulent pathogens. The OsLPL1 and OsMEK1 cDNAs share homologies with lysophospholipases and serine/threonine mitogen-activated protein (MAP) kinase kinases, respectively. The OsWRKY1 and OsEREBP1 cDNAs are homologous to transcription factors, such as the WRKY protein family and the AP2/EREBP family, respectively. Transcripts of the OsERG1, OsHin1, and OsMEK1 genes were specifically elevated only in response to the avirulent race KJ301 of the rice blast fungus. Our study yielded a number of elicitor-responsive genes that will not only provide molecular probes, but also contribute to our understanding of host defense mechanisms against the rice blast fungus.

  7. Effects of phytoestrogens on growth-related and lipogenic genes in rainbow trout (Oncorhynchus mykiss).

    Science.gov (United States)

    Cleveland, Beth M; Manor, Meghan L

    2015-04-01

    This study determined whether estradiol (E2) or the phytoestrogens genistein and daidzein regulate expression of growth-related and lipogenic genes in rainbow trout. Juvenile fish (5 mon, 65.8±1.8 g) received intraperitoneal injections of E2, genistein, or daidzein (5 μg/g body weight) or a higher dose of genistein (50 μg/g body weight). Liver and white muscle were harvested 24h post-injection. In liver, expression of vitellogenin (vtg) and estrogen receptor alpha (era1) increased in all treatments and reflected treatment estrogenicity (E2>genistein (50 μg/g)>genistein (5 μg/g)=daidzein (5 μg/g)). Estradiol and genistein (50 μg/g) reduced components of the growth hormone (GH)/insulin-like growth factor (IGF) axis in liver, including increased expression of IGF binding protein-2b1 (igfbp2b1) and reduced igfbp5b1. In liver E2 and genistein (50 μg/g) affected expression of components of the transforming growth factor beta signaling mechanism, reduced expression of ppar and rxr transcription factors, and increased expression of fatty acid synthesis genes srebp1, acly, fas, scd1, and gpat and lipid binding proteins fabp3 and lpl. In muscle E2 and genistein (50 μg/g) increased era1 and erb1 expression and decreased erb2 expression. Other genes responded to phytoestrogens in a manner that suggested regulation by estrogen receptor-independent mechanisms, including increased ghr2, igfbp2a, igfbp4, and igfbp5b1. Expression of muscle regulatory factors pax7 and myod was increased by E2 and genistein. These data indicate that genistein and daidzein affect expression of genes in rainbow trout that regulate physiological mechanisms central to growth and nutrient retention.

  8. Effect of Cottonseed Meal Fermented with Yeast on the Lipid-related Gene Expression in Broiler Chickens

    Directory of Open Access Journals (Sweden)

    CX Nie

    2015-12-01

    Full Text Available ABSTRACT Fermented cottonseed meal (FCSM is widely used in poultry diets in China. This study was conducted to investigate the effect of FCSM on lipid-related gene expression in broilers. Initially, 180 broiler chickens (21-days-old, equal number of males and females were randomly divided into three groups, with six pens per group and 10 birds per pen. The chickens in the control group were fed a diet containing unfermented cottonseed meal, and those in the treatment groups were fed with diets including either CSM fermented by Candida tropicalis (Ct group or CSM fermented by Candida tropicalis plus Saccharomyces cerevisae (Ct-Sc group until 64 days old. The results revealed that, compared with the control group (p0.05. Likewise, the expressions of peroxisome proliferator-activated receptor gamma (PPAR-g and LPL in the abdominal fat were not altered by the FCSM-supplemented diets (p>0.05. The results in this study indicate that CSM fermented by Candida tropicalis and Saccharomyces cerevisiaeeffectively regulated the genes involved in fatty acid b-oxidation and triglyceride hydrolysis in male broiler chickens. Furthermore, the effects of the FCSM-supplemented diets were significantly different between bird sexes and between yeast strains used in the fermentation process.

  9. Correlation between haplotype of apolipoprotein B gene and natural longevity persons in Uygur Nationality

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    This paper investigated the correlation between polymorphisms and haplotypes in the apolipoprotein B (apoB) gene (SP-I/D, XbaI-RFLP, VNTR) and natural longevity persons among the Uygur people in Xin-jiang. For this purpose, 191 healthy Uygur individuals aged above 90 from Hetian area of Xinjiang were recruited, and another 53 persons aged 65—70 from the same nationality, the same region and with the same gender ratio, served as the control group. Genotyping was performed by PCR-SSP, PCR-RFLP and PCR-sequencing methods. Logistic regression analyses revealed that the frequencies of X+X+ genotype, M and L alleles and the genetypes composed of M and L were significantly higher in the longevity group than in the control group. In haplotype analyses, we found that, in the long-lived people, the frequency of haplotypes composed of the X+ and M alleles was significantly higher whereas the frequency of haplotypes composed of the X- and S alleles was significantly lower (both P<0.05) I than those of their controls. These results indicated that the S allele, SS genotype and X+-S, D-S, D-X+-S haplotypes were the possible adverse factors, whereas the M, L alleles, X+X+, MM, ML, LL genotypes and I-X+-M, X+-M haplotypes were the possibe protective factors for the naturally long-lived Uygur people in China.

  10. Correlation between haplotype of apolipoprotein B gene and natural longevity persons in Uygur Nationality

    Institute of Scientific and Technical Information of China (English)

    JIANG WenXi; QIU ChangChun; CHENG ZuHeng; ZHOU WenYu; GU MingLiang; XU Qun; FANG MingWu; NIU WenQuan

    2007-01-01

    This paper investigated the correlation between polymorphisms and haplotypes in the apolipoprotein B (apoB) gene (SP-I/D, XbaI-RFLP, VNTR) and natural longevity persons among the Uygur people in Xinjiang. For this purpose, 191 healthy Uygur individuals aged above 90 from Hetian area of Xinjiang were recruited, and another 53 persons aged 65-70 from the same nationality, the same region and with the same gender ratio, served as the control group. Genotyping was performed by PCR-SSP, PCR-RFLP and PCR-sequencing methods. Logistic regression analyses revealed that the frequencies of X+X+ genotype, M and L alleles and the genetypes composed of M and L were significantly higher in the longevity group than in the control group. In haplotype analyses, we found that, in the long-lived people, the frequency of haplotypes composed of the X+ and M alleles was significantly higher whereas the frequency of haplotypes composed of the X- and S alleles was significantly lower (both P<0.05) I than those of their controls. These results indicated that the S allele, SS genotype and X+-S, D-S, D-X+-S haplotypes were the possible adverse factors, whereas the M, L alleles, X+X+, MM, ML, LL genotypes and I-X+-M, X+-M haplotypes were the possibe protective factors for the naturally long-lived Uygur people in China.

  11. Expression liver-directed genes by employing synthetic transcriptional control units

    Institute of Scientific and Technical Information of China (English)

    Marie-Luise Lemken; Wolfgang A. Wybranietz; Ulrike Schmidt; Florian Graepler; Sorin Armeanu; Michael Bitzer; Ulrich M. Lauer

    2005-01-01

    AIM: To generate and characterize the synthetic transcriptional control units for transcriptional targeting of the liver,thereby compensating for the lack of specificity of currently available gene therapeutic vector systems.METHODS: Synthetic transcriptional control unit constructs were generated and analyzed for transcriptional activities in different cell types by FACS quantification, semi-quantitative RT-PCR, and Western blotting. RESULTS: A new bifunctionally-enhanced green fluorescent protein (EGFP)/neor fusion gene cassette was generated,and could flexibly be used both for transcript quantification and for selection of stable cell clones. Then, numerous synthetic transcriptional control units consisting of a minimal promoter linked to "naturally" derived composite enhancer elements from liver-specific expressed genes or binding sites of liver-specific transcription factors were inserted upstream of this reporter cassette. Following liposome-mediated transfection, EGFP reporter protein quantification by FACS analysis identified constructs encoding multimerized composite elements of the apolipoprotein B100 (ApoB) promoter or the ornithin transcarbamoylase (OTC) enhancer to exhibit maximum transcriptional activities in liver originating cell lines, but only background levels in non-liver originating cell lines. In contrast, constructs encoding only singular binding sites of liver-specific transcription factors, namely hepatocyte nuclear factor (HNF)1, HNF3, HNF4, HNF5, or CAAT/enhancer binding protein (C/EBP) only achieved background levels of EGFP expression. Finally, both semi-quantitative RT-PCR and Western blotting analysis of Hep3B cells demonstrated maximum transcriptional activities for a multimeric 4xApoB cassette construct, which fully complied with the data obtained by initial FACS analysis.CONCLUSION: Synthetic transcriptional control unit constructs not only exhibit a superb degree of structural compactness, but also provide new means for liver

  12. Structure, Function, and Regulation of the Aldouronate Utilization Gene Cluster from Paenibacillus sp. Strain JDR-2▿

    Science.gov (United States)

    Chow, Virginia; Nong, Guang; Preston, James F.

    2007-01-01

    Direct bacterial conversion of the hemicellulose fraction of hardwoods and crop residues to biobased products depends upon extracellular depolymerization of methylglucuronoxylan (MeGAXn), followed by assimilation and intracellular conversion of aldouronates and xylooligosaccharides to fermentable xylose. Paenibacillus sp. strain JDR-2, an aggressively xylanolytic bacterium, secretes a multimodular cell-associated GH10 endoxylanase (XynA1) that catalyzes depolymerization of MeGAXn and rapidly assimilates the principal products, β-1,4-xylobiose, β-1,4-xylotriose, and MeGAX3, the aldotetrauronate 4-O-methylglucuronosyl-α-1,2-xylotriose. Genomic libraries derived from this bacterium have now allowed cloning and sequencing of a unique aldouronate utilization gene cluster comprised of genes encoding signal transduction regulatory proteins, ABC transporter proteins, and the enzymes AguA (GH67 α-glucuronidase), XynA2 (GH10 endoxylanase), and XynB (GH43 β-xylosidase/α-arabinofuranosidase). Expression of these genes, as well as xynA1 encoding the secreted GH10 endoxylanase, is induced by growth on MeGAXn and repressed by glucose. Sequences in the yesN, lplA, and xynA2 genes within the cluster and in the distal xynA1 gene show significant similarity to catabolite responsive element (cre) defined in Bacillus subtilis for recognition of the catabolite control protein (CcpA) and consequential repression of catabolic regulons. The aldouronate utilization gene cluster in Paenibacillus sp. strain JDR-2 operates as a regulon, coregulated with the expression of xynA1, conferring the ability for efficient assimilation and catabolism of the aldouronate product generated by a multimodular cell surface-anchored GH10 endoxylanase. This cluster offers a desirable metabolic potential for bacterial conversion of hemicellulose fractions of hardwood and crop residues to biobased products. PMID:17921311

  13. Digital gene-expression profiling analysis of the cholesterol-lowering effects of alfalfa saponin extract on laying hens.

    Directory of Open Access Journals (Sweden)

    Lu Zhou

    Full Text Available BACKGROUND: To prevent cardiovascular disease, people are advised to limit their intake of dietary cholesterol to less than 300 mg/day. Egg consumption has been seriously reduced because of the high levels of cholesterol. The purpose of the present study was to evaluate the cholesterol-lowering effects of alfalfa saponin extract (ASE in yolk and the molecular mechanisms underlying these effects using digital gene-expression profiling analysis. Liver and ovary tissues were isolated from laying hens fed with ASE for RNA sequencing. RESULTS: The cholesterol content of the yolks of eggs from hens fed 120 mg/kg ASE declined considerably on day 60. Other groups (60, 240, 480 mg/kg ASE group also showed decreases, but they were not significant. Digital gene expression generated over nine million reads per sample, producing expression data for least 12,384 genes. Among these genes, 110 genes showed greater than normal expression in the liver and 107 genes showed greater than normal expression in the ovary. Cholesterol 7 alpha-hydroxylase (Cyp7a1 and apolipoprotein H (Apoh, which act in the synthesis of bile acid and cholesterol efflux, showed more expression in the livers of hens given dietary ASE supplementation. In the ovary, levels of very low density lipoprotein receptor (Vldlr, apolipoprotein B (Apob, apovitellenin 1 (ApovldlII and vitellogenin (VtgI, VtgII and VtgIII in ovary decreased with dietary ASE supplementation. CONCLUSION: Transcriptome analysis revealed that the molecular mechanisms underlying the cholesterol-lowering effects of ASE were partially mediated by enhancement of cholesterol efflux in the liver and this reduced of cholesterol deposition in the ovary.

  14. Gene network and pathway analysis of bovine mammary tissue challenged with Streptococcus uberis reveals induction of cell proliferation and inhibition of PPARγ signaling as potential mechanism for the negative relationships between immune response and lipid metabolism

    Directory of Open Access Journals (Sweden)

    Rodriguez-Zas Sandra L

    2009-11-01

    Full Text Available Abstract Background Information generated via microarrays might uncover interactions between the mammary gland and Streptococcus uberis (S. uberis that could help identify control measures for the prevention and spread of S. uberis mastitis, as well as improve overall animal health and welfare, and decrease economic losses to dairy farmers. The main objective of this study was to determine the most affected gene networks and pathways in mammary tissue in response to an intramammary infection (IMI with S. uberis and relate these with other physiological measurements associated with immune and/or metabolic responses to mastitis challenge with S. uberis O140J. Results Streptococcus uberis IMI resulted in 2,102 (1,939 annotated differentially expressed genes (DEG. Within this set of DEG, we uncovered 20 significantly enriched canonical pathways (with 20 to 61 genes each, the majority of which were signaling pathways. Among the most inhibited were LXR/RXR Signaling and PPARα/RXRα Signaling. Pathways activated by IMI were IL-10 Signaling and IL-6 Signaling which likely reflected counter mechanisms of mammary tissue to respond to infection. Of the 2,102 DEG, 1,082 were up-regulated during IMI and were primarily involved with the immune response, e.g., IL6, TNF, IL8, IL10, SELL, LYZ, and SAA3. Genes down-regulated (1,020 included those associated with milk fat synthesis, e.g., LPIN1, LPL, CD36, and BTN1A1. Network analysis of DEG indicated that TNF had positive relationships with genes involved with immune system function (e.g., CD14, IL8, IL1B, and TLR2 and negative relationships with genes involved with lipid metabolism (e.g., GPAM, SCD, FABP4, CD36, and LPL and antioxidant activity (SOD1. Conclusion Results provided novel information into the early signaling and metabolic pathways in mammary tissue that are associated with the innate immune response to S. uberis infection. Our study indicated that IMI challenge with S. uberis (strain O140J elicited

  15. Carbenoxolone alters the morphology of adipose tissues and downregulates genes involved in adipogenesis, glucose transport and lipid metabolism in high-fat diet-fed mice.

    Science.gov (United States)

    Sano, S; Nakagawa, Y; Yamaguchi, R; Fujisawa, Y; Satake, E; Nagata, E; Nakanishi, T; Liu, Y-J; Ohzeki, T

    2012-01-01

    Glucocorticoid (GC) excess promotes adipose tissue accumulation, and 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) plays an important role in the local amplification of GC. Therefore, in this study, we investigated the effects of carbenoxolone (CBX), an 11β-HSD1 inhibitor, on morphological changes in visceral fat, and the expression of genes involved in adipogenesis and lipid metabolism in high-fat (HF) diet-fed mice. Mice were fed a HF diet from 5 weeks of age. At 10 weeks of age, the mice received an intraperitoneal injection of CBX or vehicle every day for 2 weeks. CBX decreased body weight and visceral fat mass, and improved insulin sensitivity in HF-fed mice. This was accompanied by reduced adipocyte size and a decrease in large-sized adipocytes in visceral fat. The expression of adipogenesis (PPARγ and C/EBPα), glucose transport (GLUT4) and lipid metabolism (LPL, ATGL, and HSL)-related genes were suppressed in CBX mice. CBX treatment induced beneficial morphological changes in visceral fat and decreased the expression of adipogenesis, glucose transport and lipid metabolism-related genes. These findings reveal a potential mechanism underling the effects of CBX on reduced fat accumulation and improved insulin sensitivity. © Georg Thieme Verlag KG Stuttgart · New York.

  16. 中国人群脂蛋白脂肪酶基因突变与高脂血症的相关性研究%Genetic Screening of the Lipoprotein Lipase Gene for Mutations in Chinese Subjects with or without Hypertriglyceridemia

    Institute of Scientific and Technical Information of China (English)

    杨宇虹; 穆云祥; 赵郁; 刘新宇; 赵莉莉; 汪军梅; 解用虹

    2007-01-01

    Objective: To investigate the association between the mutations in lipoprotein lipase gene and hypertriglyceridemia (HTG). Methods: The lipoprotein lipase (LPL) gene was screened for mutations in 386 Chinese subjects with (108 cases in the HTG group) or without HTG (278 cases in the control group), by single-strand conformation polymorphism (SSCP) analysis and DNA sequencing. Results: One novel silent mutation L103L, one missense mutation P207L, three splicing mutations Int3/3' -ass/C(-6)→T, and the common S447X polymorphism has been identified in the whole coding region and exon-intron junctions of the LPL gene were examined. Heterozygous P207L found in the HTG group was the first case reported in Asia and subsequently another P207L heterozygote was found in the proband's family, all of which suggested that P207L was one of the causes of familial combined hyperlipidemia, but was not so prevalent as that in French Canadian. Int3/3'-ass/C(-6)→T was found in both groups in the present study although it was regarded as a pathogenic variant to HTG earlier on. Moreover about the beneficial polymorphism S447X,there was also some supportive evidence that the levels of triglycerides (TG) in S447X carriers were significantly lower than noncarriers in the subjects without HTG. Conclusions: The association between the LPL variants and HTG is quite complicated and versatile, genotyping of LPL in a larger-scale screening should be necessary and justifiable.%为进行脂蛋白脂肪酶基因突变与中国人群高脂血症的相关性研究,采用单链构象多态性分析结合DNA序列测定的方法,对386例(其中108例高脂血症患者,278例正常对照)中国人群进行突变筛查.结果发现1个新的沉默突变L103L,1个错义突变P207L,3个剪接突变Int3/3'-ass/C(-6)→T和普遍存在的S447X多态性,其中发生在高脂血症组的P207L杂合子为亚洲首报,并对先证者的家系进行了研究,认为P207L是家族性高脂血症的病因之

  17. 影响猪肉质的主效基因和候选基因%Progress in major and candidate genes influencing meat quality traits in pigs

    Institute of Scientific and Technical Information of China (English)

    李凤; 黄业传; 吴照明

    2012-01-01

    Abstract.. More attention was paid on meat quality by both consumers and producers. Meat quality traits influenced its economical value directly. The high development of molecular biology had stimulated people's care and accelerated their study for genes concerning meat quality. In this paper,the research advance of major genes such as hal gene, PRKAG3 gene, rendement napole gene(RN) and of candidate gene such as fat acid binding protein (FABPs),hormone-sensitive lipase gene (HSL),lipoprotein lipase gene (LPL) were reviewed.%摘要:猪肉的品质问题已经引起了生产者和消费者的普遍关注,肉质性状直接影响到肉品的食用价值和经济价值。分子生物学技术的快速发展也促进了人们对于影响肉质相关基因的重视和研究。本文综述了与肉质相关的主效基因(MajorGene)烷氟基因(Halgene)、单磷酸腺苷蛋白激酶(AMPK)γ3亚基基因(PRKAG3)和酸肉基因(RendementNapoleGene,RN)以及脂肪酸结合蛋白基因(FatAcidBindingProteinFABPs)、激素敏感脂肪酶(Hormone—SensitiveLipase.HSL)基因和脂蛋白脂肪酶(LipoproteinLipase.LPL)基因等候选基因(candidategene)的研究进展。

  18. The molecular basis of familial hypercholesterolemia in Lebanon: spectrum of LDLR mutations and role of PCSK9 as a modifier gene.

    Science.gov (United States)

    Abifadel, Marianne; Rabès, Jean-Pierre; Jambart, Sélim; Halaby, Georges; Gannagé-Yared, Marie-Hélène; Sarkis, Antoine; Beaino, Ghada; Varret, Mathilde; Salem, Nabiha; Corbani, Sandra; Aydénian, Hermine; Junien, Claudine; Munnich, Arnold; Boileau, Catherine

    2009-07-01

    Autosomal dominant hypercholesterolemia (ADH), a major risk for coronary heart disease, is associated with mutations in the genes encoding the low-density lipoproteins receptor (LDLR), its ligand apolipoprotein B (APOB) or PCSK9 (Proprotein Convertase Subtilin Kexin 9). Familial hypercholesterolemia (FH) caused by mutation in the LDLR gene is the most frequent form of ADH. The incidence of FH is particularly high in the Lebanese population presumably as a result of a founder effect. In this study we characterize the spectrum of the mutations causing FH in Lebanon: we confirm the very high frequency of the LDLR p.Cys681X mutation that accounts for 81.5 % of the FH Lebanese probands recruited and identify other less frequent mutations in the LDLR. Finally, we show that the p.Leu21dup, an in frame insertion of one leucine to the stretch of 9 leucines in exon 1 of PCSK9, known to be associated with lower LDL-cholesterol levels in general populations, is also associated with a reduction of LDL-cholesterol levels in FH patients sharing the p.C681X mutation in the LDLR. Thus, by studying for the first time the impact of PCSK9 polymorphism on LDL-cholesterol levels of FH patients carrying a same LDLR mutation, we show that PCSK9 might constitute a modifier gene in familial hypercholesterolemia.

  19. Gene therapy

    Institute of Scientific and Technical Information of China (English)

    2005-01-01

    2005147 CNHK200-hA-a gene-viral therapeutic system and its antitumor effect on lung cancer. WANG Wei-guo(王伟国),et al. Viral & Gene Ther Center, Eastern Hepatobilli Surg Instit 2nd Milit Univ, Shanghai 200438. Chin J Oncol,2005:27(2):69-72. Objective: To develop a novel vector system, which combines the advantages of the gene therapy,

  20. Fenofibrate increases very low density lipoprotein triglyceride production despite reducing plasma triglyceride levels in APOE*3-Leiden.CETP mice.

    Science.gov (United States)

    Bijland, Silvia; Pieterman, Elsbet J; Maas, Annemarie C E; van der Hoorn, José W A; van Erk, Marjan J; van Klinken, Jan B; Havekes, Louis M; van Dijk, Ko Willems; Princen, Hans M G; Rensen, Patrick C N

    2010-08-13

    The peroxisome proliferator-activated receptor alpha (PPARalpha) activator fenofibrate efficiently decreases plasma triglycerides (TG), which is generally attributed to enhanced very low density lipoprotein (VLDL)-TG clearance and decreased VLDL-TG production. However, because data on the effect of fenofibrate on VLDL production are controversial, we aimed to investigate in (more) detail the mechanism underlying the TG-lowering effect by studying VLDL-TG production and clearance using APOE*3-Leiden.CETP mice, a unique mouse model for human-like lipoprotein metabolism. Male mice were fed a Western-type diet for 4 weeks, followed by the same diet without or with fenofibrate (30 mg/kg bodyweight/day) for 4 weeks. Fenofibrate strongly lowered plasma cholesterol (-38%) and TG (-60%) caused by reduction of VLDL. Fenofibrate markedly accelerated VLDL-TG clearance, as judged from a reduced plasma half-life of glycerol tri[(3)H]oleate-labeled VLDL-like emulsion particles (-68%). This was associated with an increased post-heparin lipoprotein lipase (LPL) activity (+110%) and an increased uptake of VLDL-derived fatty acids by skeletal muscle, white adipose tissue, and liver. Concomitantly, fenofibrate markedly increased the VLDL-TG production rate (+73%) but not the VLDL-apolipoprotein B (apoB) production rate. Kinetic studies using [(3)H]palmitic acid showed that fenofibrate increased VLDL-TG production by equally increasing incorporation of re-esterified plasma fatty acids and liver TG into VLDL, which was supported by hepatic gene expression profiling data. We conclude that fenofibrate decreases plasma TG by enhancing LPL-mediated VLDL-TG clearance, which results in a compensatory increase in VLDL-TG production by the liver.

  1. Trichoderma genes

    Science.gov (United States)

    Foreman, Pamela [Los Altos, CA; Goedegebuur, Frits [Vlaardingen, NL; Van Solingen, Pieter [Naaldwijk, NL; Ward, Michael [San Francisco, CA

    2012-06-19

    Described herein are novel gene sequences isolated from Trichoderma reesei. Two genes encoding proteins comprising a cellulose binding domain, one encoding an arabionfuranosidase and one encoding an acetylxylanesterase are described. The sequences, CIP1 and CIP2, contain a cellulose binding domain. These proteins are especially useful in the textile and detergent industry and in pulp and paper industry.

  2. Apolipoprotein B100 is required for hepatitis C infectivity and Mipomersen inhibits hepatitis C

    Science.gov (United States)

    Schaefer, Esperance A K; Meixiong, James; Mark, Christina; Deik, Amy; Motola, Daniel L; Fusco, Dahlene; Yang, Andrew; Brisac, Cynthia; Salloum, Shadi; Lin, Wenyu; Clish, Clary B; Peng, Lee F; Chung, Raymond T

    2016-01-01

    AIM To characterize the role of apolipoprotein B100 (apoB100) in hepatitis C viral (HCV) infection. METHODS In this study, we utilize a gene editing tool, transcription activator-like effector nucleases (TALENs), to generate human hepatoma cells with a stable genetic deletion of APOB to assess of apoB in HCV. Using infectious cell culture-competent HCV, viral pseudoparticles, replicon models, and lipidomic analysis we determined the contribution of apoB to each step of the viral lifecycle. We further studied the effect of mipomersen, an FDA-approved antisense inhibitor of apoB100, on HCV using in vitro cell-culture competent HCV and determined its impact on viral infectivity with the TCID50 method. RESULTS We found that apoB100 is indispensable for HCV infection. Using the JFH-1 fully infectious cell-culture competent virus in Huh 7 hepatoma cells with TALEN-mediated gene deletion of apoB (APOB KO), we found a significant reduction in HCV RNA and protein levels following infection. Pseudoparticle and replicon models demonstrated that apoB did not play a role in HCV entry or replication. However, the virus produced by APOB KO cells had significantly diminished infectivity as measured by the TCID-50 method compared to wild-type virus. Lipidomic analysis demonstrated that these virions have a fundamentally altered lipidome, with complete depletion of cholesterol esters. We further demonstrate that inhibition of apoB using mipomersen, an FDA-approved anti-sense oligonucleotide, results in a potent anti-HCV effect and significantly reduces the infectivity of the virus. CONCLUSION ApoB is required for the generation of fully infectious HCV virions, and inhibition of apoB with mipomersen blocks HCV. Targeting lipid metabolic pathways to impair viral infectivity represents a novel host targeted strategy to inhibit HCV. PMID:28018102

  3. Association between polymorphisms in genes involved in lipid metabolism and immunological status in chronically HIV-infected patients.

    Science.gov (United States)

    Echeverria, Patricia; Guardiola, Montse; González, Marta; Vallvé, Joan Carles; Bonjoch, Anna; Puig, Jordi; Clotet, Bonaventura; Ribalta, Josep; Negredo, Eugènia

    2015-02-01

    Several studies have reported associations between lipid parameters and clinical progression of HIV infection. We performed a cross-sectional study including 468 antiretroviral-treated HIV-infected patients to investigate the impact of 13 polymorphisms of 9 genes affecting lipid metabolism and CD4 and CD8-T cell levels. Polymorphisms were identified in genes selected for their role in the development of atherogenic dyslipidemia, defined as triglycerides ⩾1.7mmol/L and high-density lipoprotein cholesterol (HDLc) <1.02 in women or 1.28mmol/L in men. Lipid and lipoprotein parameters were determined in all participants, as well as CD4 and CD8 T-cell counts. ANOVA was performed to compare the mean values of lipid and CD4 and CD8 T-cell count data. A Bonferroni correction for multiple comparisons was applied. 468 patients were included, 148 of them had a diagnosis of atherogenic dyslipidemia. The polymorphism rs3135506 in APOA5 was associated with a 9% increase in triglycerides (p=0.002), 10% and 21% decrease in HDLc (p=0.005), and CD4 T-cell count (p=0.024), respectively. APOA5 rs662799, was associated with a 19% increase in CD8 T-cell count (p=0.002). Carriers of LPL rs328 in the dyslipidemic group presented 11% higher levels of HDLc (p=0.015) and 14% higher levels of CD4 cells (p=0.038). In conclusion, polymorphisms in genes associated to the development of atherogenic dyslipidemia, especially variants in APOA5 gene (rs3135506 and rs662799), can influence the circulating CD4 T-cell levels in chronically HIV-infected patients. These data support previous reports on the effect of lipid metabolism on immunologic parameters in HIV+ individuals on antiretroviral therapy.

  4. Swertiamarin: An Active Lead from Enicostemma littorale Regulates Hepatic and Adipose Tissue Gene Expression by Targeting PPAR-γ and Improves Insulin Sensitivity in Experimental NIDDM Rat Model

    Directory of Open Access Journals (Sweden)

    Tushar P. Patel

    2013-01-01

    Full Text Available Enicostemma littorale (EL Blume is one of the herbs widely used for treating and alleviating the effects of both type I and type II diabetes. However, lack of understanding of mechanism precludes the use of the herb and its molecules. In this study, we attempt to unravel the molecular mechanism of action of swertiamarin, a compound isolated form EL, by comparing its molecular effects with those of aqueous EL extract in alleviating the insulin resistance in type II diabetes. We further investigated hypolipidemic and insulin sensitizing effect of swertiamarin in experimentally induced noninsulin dependent diabetes mellitus (NIDDM in rats. Swertiamarin (50 mg/kg and aqueous extract (15 grams dried plant equivalent extract/kg were administered to rats orally for 40 days and tight regulation of serum glucose, insulin, and lipid profile was found in both groups. Their mode of action was by restoring G6Pase and HMG-CoA reductase activities to normal levels and restoring normal transcriptional levels of PEPCK, GK, Glut 2, PPAR-γ, leptin, adiponectin, LPL, SREBP-1c, and Glut 4 genes. This suggests that both treatments increased insulin sensitivity and regulated carbohydrate and fat metabolism. This is the first report on the role of SM in regulating the PPARγ-mediated regulation of candidate genes involved in metabolism in peripheral tissues in vivo.

  5. Green tea polyphenols alleviate obesity in broiler chickens through the regulation of lipid-metabolism-related genes and transcription factor expression.

    Science.gov (United States)

    Huang, Jinbao; Zhang, Yong; Zhou, Yibin; Zhang, Zhengzhu; Xie, Zhongwen; Zhang, Jinsong; Wan, Xiaochun

    2013-09-11

    The current study investigated the effects of green tea polyphenols (GTPs) on lipid metabolism and its mechanisms using broiler chickens (Gallus gallus domesticus). A total of 36 male chickens (35 days old) had been subjected to an oral administration of GTPs at a dosage of 0, 50 (low), and 100 (high) mg/kg of body weight for 20 days. Our results showed that GTPs significantly decreased the abdominal and subcutaneous fat masses of broilers and reduced the serum triglyceride, total cholesterol, and low-density lipoprotein cholesterol levels compared to those of the control. Furthermore, the expression levels for lipid anabolism genes were significantly downregulated, while the expression levels of fat transportation and catabolism-related genes, carnitine palmitoyl transferase I (CPT-I), acyl-CoA oxidase 1 (ACOX1), and peroxisome proliferator-activated receptor-α (PPARα) in liver, adipose triglyceride lipase (ATGL) in abdominal fat, and lipoprotein lipase (LPL) in skeletal muscles, were notably upregulated. Our data have revealed that GTPs alleviate obesity and serum lipid levels in broiler chickens by suppressing fatty acid synthesis and stimulating lipolysis.

  6. Gene Therapy.

    Science.gov (United States)

    Thorne, Barb; Takeya, Ryan; Vitelli, Francesca; Swanson, Xin

    2017-03-14

    Gene therapy refers to a rapidly growing field of medicine in which genes are introduced into the body to treat or prevent diseases. Although a variety of methods can be used to deliver the genetic materials into the target cells and tissues, modified viral vectors represent one of the more common delivery routes because of its transduction efficiency for therapeutic genes. Since the introduction of gene therapy concept in the 1970s, the field has advanced considerably with notable clinical successes being demonstrated in many clinical indications in which no standard treatment options are currently available. It is anticipated that the clinical success the field observed in recent years can drive requirements for more scalable, robust, cost effective, and regulatory-compliant manufacturing processes. This review provides a brief overview of the current manufacturing technologies for viral vectors production, drawing attention to the common upstream and downstream production process platform that is applicable across various classes of viral vectors and their unique manufacturing challenges as compared to other biologics. In addition, a case study of an industry-scale cGMP production of an AAV-based gene therapy product performed at 2,000 L-scale is presented. The experience and lessons learned from this largest viral gene therapy vector production run conducted to date as discussed and highlighted in this review should contribute to future development of commercial viable scalable processes for vial gene therapies.

  7. Adipogenic Gene Expression in Gilthead Sea Bream Mesenchymal Stem Cells from Different Origin

    Science.gov (United States)

    Salmerón, Cristina; Riera-Heredia, Natàlia; Gutiérrez, Joaquim; Navarro, Isabel; Capilla, Encarnación

    2016-01-01

    During the last decades, adipogenesis has become an emerging field of study in aquaculture due to the relevance of the adipose tissue in many physiological processes and its connection with the endocrine system. In this sense, recent studies have translated into the establishment of preadipocyte culture models from several fish species, sometimes lacking information on the mRNA levels of adipogenic genes. Thus, the aim of this study was to determine the gene expression profile of gilthead sea bream (Sparus aurata) primary cultured mesenchymal stem cells (MSCs) from different origin (adipose tissue and vertebra bone) during adipogenesis. Both cell types differentiated into adipocyte-like cells, accumulating lipids inside their cytoplasm. Adipocyte differentiation of MSCs from adipose tissue resulted in downregulation of several adipocyte-related genes (such as lpl, hsl, pparα, pparγ and gapdh2) at day 4, gapdh1 at day 8, and fas and pparβ at day 12. In contrast, differences in lxrα mRNA expression were not observed, while g6pdh levels increased during adipocyte maturation. Gapdh and Pparγ protein levels were also detected in preadipocyte cultures; however, only the former increased its expression during adipogenesis. Moreover, differentiation of bone-derived cells into adipocytes also resulted in the downregulation of several adipocyte gene markers, such as fas and g6pdh at day 10 and hsl, pparβ, and lxrα at day 15. On the other hand, the osteogenic genes fib1a, mgp, and op remained stable, but an increase in runx2 expression at day 20 was observed. In summary, the present study demonstrates that gilthead sea bream MSCs, from both adipose tissue and bone, differentiate into adipocyte-like cells, although revealed some kind of species- and cell lineage-specific regulation with regards to gene expression. Present data also provide novel insights into some of the potential key genes controlling adipogenesis in gilthead sea bream that can help to better

  8. Adipogenic gene expression in gilthead sea bream mesenchymal stem cells from different origin

    Directory of Open Access Journals (Sweden)

    Cristina Salmerón

    2016-08-01

    Full Text Available During the last decades, adipogenesis has become an emerging field of study in aquaculture due to the relevance of the adipose tissue in many physiological processes and its connection with the endocrine system. In this sense, recent studies have translated into the establishment of preadipocyte culture models from several fish species, lacking sometimes information on the mRNA levels of adipogenic genes. Thus, the aim of this study was to determine the gene expression profile of gilthead sea bream (Sparus aurata primary cultured mesenchymal stem cells (MSCs from different origin (adipose tissue and vertebra bone during adipogenesis. Both cell types differentiated into adipocyte-like cells accumulating lipids inside their cytoplasm. Adipocyte differentiation of MSCs from adipose tissue resulted in down-regulation of several adipocyte-related genes (such as lpl, hsl, pparα, pparγ and gapdh2 at day 4, gapdh1 at day 8, and fas and pparβ at day 12. In contrast, differences in lxrα mRNA expression were not observed, while g6pdh levels increased during adipocyte maturation. Gapdh and Pparγ protein levels were also detected in preadipocyte cultures; however, only the former increased its expression during adipogenesis. Moreover, differentiation of bone-derived cells into adipocytes also resulted in the down-regulation of several adipocyte gene markers such as fas and g6pdh at day 10 and hsl, pparβ and lxrα at day 15. On the other hand, the osteogenic genes fib1a, mgp and op remained stable, but an increase in runx2 expression at day 20 was observed. In summary, the present study demonstrates that gilthead sea bream MSCs from both adipose tissue and bone differentiate into adipocyte-like cells, although revealed some kind of species- and cell lineage-specific regulation with regards to gene expression. Present data also provide novel insights into some of the potential key genes controlling adipogenesis in gilthead sea bream that can help to

  9. SREBP-1c Gene Silencing can Decrease Lipid Deposits in Bovine Hepatocytes Cultured in Vitro

    Directory of Open Access Journals (Sweden)

    Qinghua Deng

    2014-05-01

    Full Text Available Background: Fatty liver is a major metabolic disorder that occurs during early lactation in high-producing dairy cows. Sterol regulatory element-binding protein-1c (SREBP-1c is an important transcription factor that regulates lipid synthesis by regulating the expression of lipid metabolism genes. Methods: In this study, we reduced the expression of SREBP-1c by adenovirus-mediated SREBP-1c with a low expression vector (AD-GFP-SREBP-1c to study the effects of SREBP-1c on lipid deposits in bovine hepatocytes. The expression levels and enzyme activities of SERBP-1c and its target genes were determined by real-time PCR, western blot, and ELISA. Results: These results showed that Ad-GFP-SREBP-1c could inhibit SREBP-1c expression. The expression of the lipid synthesis enzyme acetyl-CoA carboxylase (ACC was down-regulated. The expression levels of the lipid oxidation enzymes long-chain fatty acyl-COA synthetase (ACSL-1, carnitine palmitoyltransferase І (CPT-І, carnitine palmitoyltransferase II (CPT- II, and β-hydroxyacyl-CoA-DH (HADH were significantly elevated. Furthermore, the expression levels of factors involved in the assembly and transport of very low-density lipoproteins (VLDLs, such as apolipoprotein B100 (ApoB, apolipoprotein E (ApoE, and microsomal triglyceride transfer protein (MTTP were decreased comparison with the negative control and the blank control groups, but the low-density lipoprotein receptor (LDLR was elevated. The concentrations of TG (triglyceride and VLDL were also reduced. Conclusion: These data suggest that low SREBP-1c expression can decrease lipid synthesis, increase lipid oxidation, and decrease the TG and VLDL content in bovine hepatocytes.

  10. The Expression of the Related Fatty Acid Synthesis Key Enzyme Genes in Bovine Somatic Cell%牛乳腺脂肪合成关键酶基因在乳汁体细胞中的表达研究

    Institute of Scientific and Technical Information of China (English)

    谢佳喜; 朱河水; 杨国宇; 李宏基; 郭豫杰; 汪新建; 王月影

    2011-01-01

    为了阐明乳脂合成的影响因素及其内在分子机理,为反刍动物原料乳的优化,特别是为乳脂肪的营养调控和遗传改良提供理论依据.本试验以奶牛初乳、常乳和末乳中的乳汁体细胞为研究对象,以看家基因GAPDH为内参,对初乳、常乳和末乳中LPL、CD36、VLDLR、ACSS2、ACSL1、FABP3、ACC、FASN、SCD、ADFP、XDH和BTN1A1 mRNA进行半定量RT-PCR分析.结果发现,LPL、CD36、VLDLR、ACSS2、ACSL1、FABP3、SCD、ADFP、XDH和BTN1Al mRNA在初乳、常乳和末乳中均有表达,而ACC和FASN mRNA只在初乳中表达,常乳和末乳中均不表达;半定量结果表明,与初乳相比,常乳和末乳中LPL、CD36、VLDLR、ACSS2、ACSL1、FABP3、SCD、ADFP、XDH和BTN1Al mRNA转录水平显著降低(P<0.05),且常乳与末乳间差异不显著(P>0.05).研究结果提示初乳期乳腺脂肪合成能力明显高于常乳和末乳期乳腺,且脂肪合成关键酶基因的表达与细胞内脂转运和代谢的生理变化有关.%To clarify the molecular mechanism of milk fat synthesis, optimizing ruminant raw milk, particularly providing theory basis for nutrition regulation and heredity improving for milk fat. Somatic cells in colostrum milk, mature milk and involution milk were selected and housekeeping gene GAPDH was selected as reference, the semi-quantitive RT-PCR was used to analyze the expression of LPL, CD36, VLDLR, ACSS2, ACSLl, FABP3, ACC, FASN, SCD, AD-FP, XDH and BTN1A1 mRNA in milk. The results showed that the genes LPL, CD36, VLDLR, ACSS2, ACSLl, FABP3, ACC, FASN, SCD, ADFP, XDH and BTNV1A1 mRNA expressed in the colostrum milk, mature milk and involution milk. However the genes ACC and FASN were not detected in mature milk and involution milk. The relative quantitive results showed that the expression level of LPL, CD36, VLDLR, ACSS2, ACSLl, FABP3, ACC, FASN, SCD, ADFP, XDH and BTN1A1 mRNA in mature milk and involution milk were significantly decreased(P0. 05) between mature

  11. Gene Therapy

    Science.gov (United States)

    ... or improve your body's ability to fight disease. Gene therapy holds promise for treating a wide range of diseases, such as cancer, cystic fibrosis, heart disease, diabetes, hemophilia and AIDS. Researchers are still studying how and ...

  12. Genes V.

    Energy Technology Data Exchange (ETDEWEB)

    Lewin, B.

    1994-12-31

    This fifth edition book encompasses a wide range of topics covering 1,272 pages. The book is arranged into nine parts with a total of 36 chapters. These nine parts include Introduction; DNA as a Store of Information; Translation; Constructing Cells; Control of Prokaryotypic Gene Expression; Perpetuation of DNA; Organization of the Eukaryotypic Genome; Eukaryotypic Transcription and RNA Processing; The Dynamic Genome; and Genes in Development.

  13. A novel mutation in proprotein convertase subtilisin/kexin type 9 gene leads to familial hypercholesterolemia in a Chinese family

    Institute of Scientific and Technical Information of China (English)

    LIN Jie; JIANG Zhi-sheng; WANG Lu-ya; LIU Shu; WANG Xu-min; YONG Qiang; YANG Ya; DU Lan-ping; PAN Xiao-dong; WANG Xu

    2010-01-01

    Background Familial hypercholesterolemia (FH) is an autosomal disorder associated with elevated plasma low density lipoprotein (LDL) levels leading to premature coronary heart disease (CHD). As a result of long-term hyperlipemia, FH patients will present endarterium thickening and atherosclerosis. In the present study we scanned the related gene of a clinically diagnosed autosomal genetic hypercholesterolemia family for the possible mutations and established eukaryotic expression vector of mutation of proprotein convertase subtilisin/kexin type 9 (PCSK9) gene with gene recombination technique to investigate the contributions of the variation on low density lipoprotein receptor (LDL-R) metabolism and function alternation.Methods Mutation detection was conducted for LDL-R, apolipoprotein B100 (apoB100) and PCSK9 gene with nucleotide sequencing in a Chinese FH family. The full-length cDNA of wild type PCSK9 gene (WT-PCSK9) was obtained from Bel-7402. Site mutagenesis was used to establish the recombinant eukaryotic expression vector carrying pathogenic type of PCSK9 gene and the inserted fragment was sequenced. With the blank vector as control, liposome transfection method was used to transfect the Bel-7402 cells with recombinant plasmid. The expression of LDL-R mRNA was examined by RT-PCR. PCSK9 and the expression of LDL-R protein were determined by Western blotting. Results The G→T mutation at the 918 nucleotide of PCSK9 gene resulted in the substitution of the arginine by a serine at the codon 306 of exon 6. After sequencing, it was confirmed that the inserted fragment of established expression vector had correct size and sequence and the mutant was highly expressed in Bel-7402 cells. There was no significant variation in the levels of LDL-R mRNA. LDL-R mature protein was decreased by 57% after the cells were transfected by WT-PCSK9 plasmid. Mature LDL-R was significantly decreased by 12% after the cells were transfected by R306S mutant as evidenced by gray scale

  14. The association between Mediterranean Diet Score and glucokinase regulatory protein gene variation on the markers of cardiometabolic risk: an analysis in the European Prospective Investigation into Cancer (EPIC)-Norfolk study.

    Science.gov (United States)

    Sotos-Prieto, Mercedes; Luben, Robert; Khaw, Kay-Tee; Wareham, Nicholas J; Forouhi, Nita G

    2014-07-14

    Consumption of a Mediterranean diet (MD) and genetic variation in the glucokinase regulatory protein (GCKR) gene have been reported to be associated with TAG and glucose metabolism. It is uncertain whether there is any interaction between these factors. Therefore, the aims of the present study were to test the association of adherence to a MD and rs780094 (G>A) SNP in the GCKR gene with the markers of cardiometabolic risk, and to investigate the interaction between genetic variation and MD adherence. We studied 20 986 individuals from the European Prospective Investigation into Cancer (EPIC)-Norfolk study. The relative Mediterranean Diet Score (rMED: range 0-18) was used to assess MD adherence. Linear regression was used to estimate the association between the rMED, genotype and cardiometabolic continuous traits, adjusting for potential confounders. In adjusted analyses, we observed independent associations of MD adherence and genotype with cardiometabolic risk, with the highest risk group (AA genotype; lowest rMED) having higher concentrations of TAG, total cholesterol and apoB (12·5, 2·3 and 3·1%, respectively) v. those at the lowest risk (GG genotype; highest rMED). However, the associations of MD adherence with metabolic markers did not differ by genotype, with no significant gene-diet interactions for lipids or for glycated Hb. In conclusion, we found independent associations of the rMED and of the GCKR genotype with cardiometabolic profile, but found no evidence of interaction between them.

  15. Sudden cardiac death in young adults

    DEFF Research Database (Denmark)

    Larsen, Maiken K; Nissen, Peter H; Kristensen, Ingrid B;

    2012-01-01

    Familial hypercholesterolemia (FH) is a genetic disorder that may lead to premature coronary heart disease (CHD) and sudden cardiac death (SCD). Mutations in the LDLR or APOB genes cause FH. We have screened the LDLR and the ligand-binding region of APOB genes in 52 cases of SCD. Deceased patients...... premature CHD and SCD....

  16. 中国汉族人群冠心病候选基因变异及其临床关联的地域特征%Geographical characteristics of single nucleotide polymorphism of candidate genes associated with coronary artery disease in Chinese Han population

    Institute of Scientific and Technical Information of China (English)

    王胜煌; 白锋; Muhlestein JB; 崔翰斌; 王东琦; 陈晓敏; 张宏考; 崔长琮; 陈新义; 刘新宏; 张征

    2008-01-01

    -C及(或)TG的影响不尽一致.4个SNP对三个地区汉族人群冠心病发病的影响均无统计学意义.结论 不同地域中国汉族人群冠心病危险因素(环境因素和遗传因素)存在一定异质性;候选基因SNP可预测冠心病中间表型,但对临床表型缺乏显著影响,此联系独立于地域因素.%Objective To investigate the geographical characteristics of single nucleotide polymorphism(SNP) of candidate genes associated with coronary artery disease in Chinese Han population.Methods Study population were Chinese Han nationality recruited from Xi'an,Shiyan and Ningbo districts.Patients with coronary artery disease were defined by coronary angiography with stenosis ≥ 50% and control subjects with stenosis <10%,respectively.The DNA was extracted from peripheral white blood cell by approach comprised proteinase K digestion,phenol and chloroform extraction as well as isopropanol precipitation.The SNP of ATP-binding cassette transporter(ABCA1)-G596A,cholesteryl ester transfer protein(CETP)-Taq1B,Lipoprotein lipase(LPL)-Hind Ⅲ and LPL-Pvu Ⅱ were genotyped by PCR-RFLPs,and verified by gene sequencing.Results A Total of 615 patients undertaken coronary angiography were recruited from cardiac center in Xi'an(220),Ningbo(209)and Shiyan district(186),China (mean age 60±10 years,75.9% males).Diabetes melitus was more prevalent in Xi'an Cohort population than Shiyan and Ningbo cohort(P<0.01).Plasma total cholesterol,LDL cholestcol and trigtyceride levels in Xi'an Cohort population were significantly higher,and HDL-C siginificantly lower than in Shiyan and Ningbo cohort population [HDL-C:(1.17±0.48)mmol/L vs.(1.25±0.33)mmol/L and (1.29±0.44)mmol/L,P<0.05].Distribution differences for ABCA1-G596A and CETP-Taq1B genotypes were found in Xi'an Cohort population compared to Ningbo and Shiyan cohorts(for ABCA1,Xi'an:0.24,0.53,0.23 and Shiyan:0.17,0.62,0.21 and Ningbo:0.34,0.37,0.29,for GG,AG,AA,respectively,P<0.01;and for CETP,Xi'an:0.29,0.54,0.17 and Shiyan:0

  17. Analyses of single nucleotide polymorphisms in selected nutrient-sensitive genes in weight-regain prevention: the DIOGENES study.

    Science.gov (United States)

    Larsen, Lesli H; Angquist, Lars; Vimaleswaran, Karani S; Hager, Jörg; Viguerie, Nathalie; Loos, Ruth J F; Handjieva-Darlenska, Teodora; Jebb, Susan A; Kunesova, Marie; Larsen, Thomas M; Martinez, J Alfredo; Papadaki, Angeliki; Pfeiffer, Andreas F H; van Baak, Marleen A; Sørensen, Thorkild Ia; Holst, Claus; Langin, Dominique; Astrup, Arne; Saris, Wim H M

    2012-05-01

    Differences in the interindividual response to dietary intervention could be modified by genetic variation in nutrient-sensitive genes. This study examined single nucleotide polymorphisms (SNPs) in presumed nutrient-sensitive candidate genes for obesity and obesity-related diseases for main and dietary interaction effects on weight, waist circumference, and fat mass regain over 6 mo. In total, 742 participants who had lost ≥ 8% of their initial body weight were randomly assigned to follow 1 of 5 different ad libitum diets with different glycemic indexes and contents of dietary protein. The SNP main and SNP-diet interaction effects were analyzed by using linear regression models, corrected for multiple testing by using Bonferroni correction and evaluated by using quantile-quantile (Q-Q) plots. After correction for multiple testing, none of the SNPs were significantly associated with weight, waist circumference, or fat mass regain. Q-Q plots showed that ALOX5AP rs4769873 showed a higher observed than predicted P value for the association with less waist circumference regain over 6 mo (-3.1 cm/allele; 95% CI: -4.6, -1.6; P/Bonferroni-corrected P = 0.000039/0.076), independently of diet. Additional associations were identified by using Q-Q plots for SNPs in ALOX5AP, TNF, and KCNJ11 for main effects; in LPL and TUB for glycemic index interaction effects on waist circumference regain; in GHRL, CCK, MLXIPL, and LEPR on weight; in PPARC1A, PCK2, ALOX5AP, PYY, and ADRB3 on waist circumference; and in PPARD, FABP1, PLAUR, and LPIN1 on fat mass regain for dietary protein interaction. The observed effects of SNP-diet interactions on weight, waist, and fat mass regain suggest that genetic variation in nutrient-sensitive genes can modify the response to diet. This trial was registered at clinicaltrials.gov as NCT00390637.

  18. Dietary sunflower oil modulates milk fatty acid composition without major changes in adipose and mammary tissue fatty acid profile or related gene mRNA abundance in sheep.

    Science.gov (United States)

    Castro-Carrera, T; Frutos, P; Leroux, C; Chilliard, Y; Hervás, G; Belenguer, A; Bernard, L; Toral, P G

    2015-04-01

    There are very few studies in ruminants characterizing mammary and adipose tissue (AT) expression of genes and gene networks for diets causing variations in milk fatty acid (FA) composition without altering milk fat secretion, and even less complementing this information with data on tissue FA profiles. This work was conducted in sheep in order to investigate the response of the mammary gland and the subcutaneous and perirenal AT, in terms of FA profile and mRNA abundance of genes involved in lipid metabolism, to a diet known to modify milk FA composition. Ten lactating Assaf ewes were randomly assigned to two treatments consisting of a total mixed ration based on alfalfa hay and a concentrate (60 : 40) supplemented with 0 (control diet) or 25 (SO diet) g of sunflower oil/kg of diet dry matter for 7 weeks. Milk composition, including FA profile, was analysed after 48 days on treatments. On day 49, the animals were euthanized and tissue samples were collected to analyse FA and mRNA abundance of 16 candidate genes. Feeding SO did not affect animal performance but modified milk FA composition. Major changes included decreases in the concentration of FA derived from de novo synthesis (e.g. 12:0, 14:0 and 16:0) and increases in that of long-chain FA (e.g. 18:0, c9-18:1, trans-18:1 isomers and c9,t11-CLA); however, they were not accompanied by significant variations in the mRNA abundance of the studied lipogenic genes (i.e. ACACA, FASN, LPL, CD36, FABP3, SCD1 and SCD5) and transcription factors (SREBF1 and PPARG), or in the constituent FA of mammary tissue. Regarding the FA composition of AT, the little influence of SO did not appear to be linked to changes in gene mRNA abundance (decreases of GPAM and SREBF1 in both tissues, and of PPARG in the subcutaneous depot). Similarly, the great variation between AT (higher contents of saturated FA and trans-18:1 isomers in the perirenal, and of cis-18:1, c9,t11-CLA and n-3 PUFA in the subcutaneous AT) could not be related to

  19. Elevated PLA2G7 gene promoter methylation as a gender-specific marker of aging increases the risk of coronary heart disease in females.

    Directory of Open Access Journals (Sweden)

    Danjie Jiang

    Full Text Available PLA2G7 gene product is a secreted enzyme whose activity is associated with coronary heart disease (CHD. The goal of our study is to investigate the contribution of PLA2G7 promoter DNA methylation to the risk of CHD. Using the bisulphite pyrosequencing technology, PLA2G7 methylation was measured among 36 CHD cases and 36 well-matched controls. Our results indicated that there was a significant association between PLA2G7 methylation and CHD (adjusted P = 0.025. Significant gender-specific correlation was observed between age and PLA2G7 methylation (males: adjusted r = -0.365, adjusted P = 0.037; females: adjusted r = 0.373, adjusted P = 0.035. A breakdown analysis by gender showed that PLA2G7 methylation was significantly associated with CHD in females (adjusted P = 0.003 but not in males. A further two-way ANOVA analysis showed there was a significant interaction between gender and status of CHD for PLA2G7 methylation (gender*CHD: P = 6.04E-7. Moreover, PLA2G7 methylation is associated with the levels of total cholesterols (TC, r = 0.462, P = 0.009, triglyceride (TG, r = 0.414, P = 0.02 and Apolipoprotein B (ApoB, r = 0.396, P = 0.028 in females but not in males (adjusted P>0.4. Receiver operating characteristic (ROC curves showed that PLA2G7 methylation could predict the risk of CHD in females (area under curve (AUC = 0.912, P = 2.40E-5. Our results suggest that PLA2G7 methylation changes with aging in a gender-specific pattern. The correlation between PLA2G7 methylation and CHD risk in females is independent of other parameters including age, smoking, diabetes and hypertension. PLA2G7 methylation might exert its effects on the risk of CHD by regulating the levels of TC, TG, and ApoB in females. The gender disparities in the PLA2G7 methylation may play a role in the molecular mechanisms underlying the pathophysiology of CHD.

  20. Proprotein Convertase Subtilisin/Kexin Type 9 Gene E670G Polymorphism Interacts with Alcohol Consumption to Modulate Serum Lipid Levels

    Directory of Open Access Journals (Sweden)

    Lynn Htet Htet Aung, Rui-Xing Yin, Dong-Feng Wu, Xiao-Li Cao, Xi-Jiang Hu, Lin Miao

    2013-01-01

    Full Text Available Backgroud: Both alcohol consumption and the proprotein convertase subtilisin/kexin type 9 (PCSK9 gene polymorphism modulate serum lipid levels, but their interactions on serum lipid profiles are still unknown. The present study was undertaken to detect the interactions of PCSK9 E670G polymorphism and alcohol consumption on serum lipid levels.Methods: Genotypes of the PCSK9 E670G in 1352 unrelated subjects (785 non-drinkers and 567 drinkers were determined by polymerase chain reaction and restriction fragment length polymorphism combined with gel electrophoresis, and then confirmed by direct sequencing. The interactions between PCSK9 E670G genotypes and alcohol consumption on serum lipid parameters were detected by using a factorial design covariance analysis after controlling for potential confounders.Results: The levels of serum triglyceride, high-density lipoprotein cholesterol, apolipoprotein (Apo A1, and the ratio of ApoA1 to ApoB were higher in drinkers than in non-drinkers (P < 0.01 for all, whereas the levels of total cholesterol (TC, low-density lipoprotein cholesterol (LDL-C and ApoB were lower in drinkers than in non-drinkers (P < 0.001 for all. The genotypic and allelic frequencies of PCSK9 E670G were not different between non-drinkers and drinkers (P > 0.05 for each. The subjects with AA genotype in non-drinkers had higher serum LDL-C levels than the subjects with AG genotype, whereas the subjects with AG genotype in drinkers had higher serum TC levels than the subjects with AA genotypes (P < 0.05 for each. The effects of alcohol consumption on TC and LDL-C levels depended upon genotypes, the subjects with AA genotype had lower serum TC and LDL-C levels in drinkers than in non-drinkers.Conclusions: Alcohol consumption can modify the effects of the PCSK9 E670G polymorphism on serum TC and LDL-C levels. The subjects with AA genotype of the PCSK9 E670G benefit more from alcohol consumption than the subjects with AG genotype in

  1. DREB genes

    African Journals Online (AJOL)

    Unipar

    2015-03-12

    Mar 12, 2015 ... to AP2/ERF family, dehydration-responsive element-binding protein (DREB) genes, (CitsERF01 to ... Protein sequences of DREB subfamilies belonging to group I, .... position 37, and it was present in consensus in all protein.

  2. Expression of Lipid Catabolism Genes in Diannan Small-ear Pigs with Different H-FABP Genotypes%H-FABP不同基因型对滇南小耳猪脂肪分解代谢相关基因表达的影响

    Institute of Scientific and Technical Information of China (English)

    江佳伟; 黄英; 杨明华; 潘洪彬; 高士争; 赵素梅

    2013-01-01

    本研究旨在探讨不同H-FABP基因型滇南小耳猪肌内脂肪细胞脂类代谢相关基因的表达及其与肌内脂肪细胞甘油三酯(Triglycerol,TG)含量的相关性.本研究利用试剂盒测定肌内脂肪细胞TG含量,采用RT-qPCR检测肌内脂肪细胞脂类分解代谢基因mRNA表达水平.结果显示:HH基因型个体的脂类分解代谢相关基因肉碱脂酰转移酶1(Carnitine palmitoyl transferase 1,CPT-1)、脂蛋白酯酶(Lipoprotein lipase,LPL)和过氧化物酶体增殖物激活受体γ(Preoxisome proliferator-activated receptor γ,PPARγ)3种基因mRNA表达水平均显著高于hh基因型个体(P<0.05);且CPT-1、LPL、PPARγ基因mRNA的表达量与肌内脂肪细胞TG含量呈正相关.不同H-FABP基因型影响滇南小耳猪肌内脂肪细胞中脂肪分解代谢相关基因的表达,HH基因型猪脂肪分解代谢相关基因的表达量较高,可能脂类代谢活动更强,从而相对增加了肌内脂肪沉积.%This study aimed to investigate the expression of the lipid metabolism related genes,and the association between the lipid metabolism related genes and triglyceride(TG) content in intramuscular fat cells of Diannan Small-ear pigs with different H-FABP genotypes.The kit was used to determine the triglyceride(TG) content and to investigate the level of mRNA expression of lipid catabolism genes by reverse transcription quantitative real-time PCR(RT-qPCR).The resuits showed that significantly higher expression levels of carnitine palmitoyl transferase 1 (CPT-1),lipoprotein lipase(LPL) and preoxisome proliferator-activated receptor γ(PPARγ) mRNA were found in the HH genotype individuals comparing with that in hh genotype individuals(P<0.05).The expression levels of CPT-1,LPL,PPARγ genes and TG content in intramuscular adipocytes were positively correlated.The expression of fat catabolism related genes in Diannan Small-ear pigs with different H-FABP genotypes is discrepant,the expression level of the pig

  3. Adropin induction of lipoprotein lipase expression in tilapia hepatocytes.

    Science.gov (United States)

    Lian, Anji; Wu, Keqiang; Liu, Tianqiang; Jiang, Nan; Jiang, Quan

    2016-01-01

    The peptide hormone adropin plays a role in energy homeostasis. However, biological actions of adropin in non-mammalian species are still lacking. Using tilapia as a model, we examined the role of adropin in lipoprotein lipase (LPL) regulation in hepatocytes. To this end, the structural identity of tilapia adropin was established by 5'/3'-rapid amplification of cDNA ends (RACE). The transcripts of tilapia adropin were ubiquitously expressed in various tissues with the highest levels in the liver and hypothalamus. The prolonged fasting could elevate tilapia hepatic adropin gene expression, whereas no effect of fasting was observed on hypothalamic adropin gene levels. In primary cultures of tilapia hepatocytes, synthetic adropin was effective in stimulating LPL release, cellular LPL content, and total LPL production. The increase in LPL production also occurred with parallel rises in LPL gene levels. In parallel experiments, adropin could elevate cAMP production and up-regulate protein kinase A (PKA) and PKC activities. Using a pharmacological approach, cAMP/PKA and PLC/inositol trisphosphate (IP3)/PKC cascades were shown to be involved in adropin-stimulated LPL gene expression. Parallel inhibition of p38MAPK and Erk1/2, however, were not effective in these regards. Our findings provide, for the first time, evidence that adropin could stimulate LPL gene expression via direct actions in tilapia hepatocytes through the activation of multiple signaling mechanisms.

  4. Germinated brown rice extract inhibits adipogenesis through the down-regulation of adipogenic genes in 3T3-L1 adipocytes.

    Science.gov (United States)

    Ho, Jin-Nyoung; Son, Mi-Eun; Lim, Won-Chul; Lim, Seung-Taik; Cho, Hong-Yon

    2013-09-01

    The aim of this study was to examine the anti-adipogenic effect of germinated brown rice methanol extract (GBR) in 3T3-L1 adipocytes. The GBR inhibited adipocyte differentiation was measured by Oil Red O staining and glycerol-3-phosphate dehydrogenase (GPDH) activity in a dose-dependent manner without initiating any cytotoxicity. The mRNA levels of adipogenic transcription factors such as CCAAT/enhancer binding protein (C/EBPα), proliferator-activated receptorγ (PPARγ), and sterol regulatory element-binding protein-1c (SREBP-1c), and adipogenic genes, such as fatty acid synthase (FAS), adipocyte fatty acid-binding protein (aP2), and lipoprotein lipase (LPL), were significantly down-regulated by treatment with GBR when compared to that of untreated control cells. Moreover, tumor necrosis factor-α (TNF-α) and interlukin-6 (IL-6) mRNA expressions were attenuated by GBR in mature adipocytes. These data suggest that GBR exhibits an anti-adipogenic effect through the suppression of adipogenesis in 3T3-L1 adipocytes.

  5. Myristic Acid (MA) Promotes Adipogenic Gene Expression and the Differentiation of Porcine Intramuscular Adipocyte Precursor Cells

    Institute of Scientific and Technical Information of China (English)

    LU Nai-sheng; ZHANG Yong-liang; JIANG Qing-yan; SHU Gang; XIE Qiu-ping; ZHU Xiao-tong; GAO Ping; ZHOU Gui-xuan; WANG Song-bo; WANG Li-na; XI Qian-yun

    2014-01-01

    Intramuscular fat (IMF) content is considered to be a key factor that affects the marbling, tenderness, juiciness and lfavor of pork. To investigate the effects of myristic acid (MA) on the differentiation of porcine intramuscular adipocytes, cells were isolated from longissimus dorsi muscle (LDM) and treated with 0, 10, 50 or 100μmol L-1 MA. The results showed that MA signiifcantly promotes the differentiation of intramuscular adipocytes in a dose-dependent manner. MA also led to a parallel increase in the expression of peroxisome proliferator activated receptor-γ(PPARγ) and adipose-related genes, such as glucose transporter 1 (GLUT1), lipoprotein lipase (LPL), adipocyte fatty acid binding protein 4 (FABP4/aP2), fatty acid translocase (FAT), acetyl-CoA carboxylaseα(ACCα), adipose triglyceride lipase (ATGL) and fatty acid synthase (FASN). However, no signiifcant effects of MA were observed on the expression of CAAT enhancer binding protein-α(C/EBPα) or hormone sensitive lipase (HSL). The expression of pyruvate dehydrogenase kinase 4 (PDK4) was increased by MA during the early stages of differentiation (day 1-3). In addition, MA also increased the absolute content of C14 (P<0.001) and saturated fatty acids (SFA) (P<0.05) to varying degrees, but no effects were observed on other fatty acids. These results suggest that MA might be able to enhance the IMF content of pork and increase the accumulation of myristic and myristoleic acid in muscle, which might have beneifcial implications for human health.

  6. Green tea, black tea, and epigallocatechin modify body composition, improve glucose tolerance, and differentially alter metabolic gene expression in rats fed a high-fat diet.

    Science.gov (United States)

    Chen, Nora; Bezzina, Rebecca; Hinch, Edward; Lewandowski, Paul A; Cameron-Smith, David; Mathai, Michael L; Jois, Markandeya; Sinclair, Andrew J; Begg, Denovan P; Wark, John D; Weisinger, Harrison S; Weisinger, Richard S

    2009-11-01

    The mechanisms of how tea and epigallocatechin-3-gallate (EGCG) lower body fat are not completely understood. This study investigated long-term administration of green tea (GT), black tea (BT), or isolated EGCG (1 mg/kg per day) on body composition, glucose tolerance, and gene expression related to energy metabolism and lipid homeostasis; it was hypothesized that all treatments would improve the indicators of metabolic syndrome. Rats were fed a 15% fat diet for 6 months from 4 weeks of age and were supplied GT, BT, EGCG, or water. GT and BT reduced body fat, whereas GT and EGCG increased lean mass. At 16 weeks GT, BT, and EGCG improved glucose tolerance. In the liver, GT and BT increased the expression of genes involved in fatty acid synthesis (SREBP-1c, FAS, MCD, ACC) and oxidation (PPAR-alpha, CPT-1, ACO); however, EGCG had no effect. In perirenal fat, genes that mediate adipocyte differentiation were suppressed by GT (Pref-1, C/EBP-beta, and PPAR-gamma) and BT (C/EBP-beta), while decreasing LPL, HSL, and UCP-2 expression; EGCG increased expression of UCP-2 and PPAR-gamma genes. Liver triacylglycerol content was unchanged. The results suggest that GT and BT suppressed adipocyte differentiation and fatty acid uptake into adipose tissue, while increasing fat synthesis and oxidation by the liver, without inducing hepatic fat accumulation. In contrast, EGCG increased markers of thermogenesis and differentiation in adipose tissue, while having no effect on liver or muscle tissues at this dose. These results show novel and separate mechanisms by which tea and EGCG may improve glucose tolerance and support a role for these compounds in obesity prevention.

  7. (-)-Epigallocatechin gallate enhances the expression of genes related to insulin sensitivity and adipocyte differentiation in 3T3-L1 adipocytes at an early stage of differentiation.

    Science.gov (United States)

    Sakurai, Naoko; Mochizuki, Kazuki; Kameji, Hiroyuki; Shimada, Masaya; Goda, Toshinao

    2009-10-01

    (-)-Epigallocatechin gallate (EGCG) is thought to enhance insulin sensitivity in adipocytes, although doses used in in vitro experiments have been shown to promote apoptosis. To explore the effects of EGCG on insulin sensitivity in adipocytes, the expression of genes related to insulin sensitivity and adipocyte differentiation in 3T3-L1 adipocytes were measured in response to low doses of EGCG. Increasing concentrations of low-dose EGCG were administered for 8 d to differentiating 3T3 adipocytes, either at days 0-8 (early stage) or at days 8-16 (late stage). Fat accumulation and cell activity were measured by Oil Red O staining and 1-(4,5-dimethylthiazol-2-yl)-3,5-diphenylformazan assay, respectively. The expression of genes related to insulin sensitivity and adipocyte differentiation was measured by real-time reverse transcriptase-polymerase chain reaction. Fat accumulation and cell activity in 3T3-L1 cells at the early and late stages were reduced at EGCG concentrations > or = 50 microM. However, EGCG doses of 5-10 microM reduced fat accumulation and induced the expression of genes related to insulin sensitivity (including Fabp4, Cd36, Lpl, Pck1, Acox1, Lypla3, and Ucp2) and adipocyte differentiation (Pparg1, Pparg2, Cebps, and Ppargc1a). These increases were only seen at the early, and not late, stages of differentiation. These data indicate that low doses of EGCG, despite reducing triacylglycerol accumulation, induce the expression of genes related to insulin sensitivity in the early stage of differentiation.

  8. Green tea (-)-epigallocatechin-3-gallate reduces body weight with regulation of multiple genes expression in adipose tissue of diet-induced obese mice.

    Science.gov (United States)

    Lee, Mak-Soon; Kim, Chong-Tai; Kim, Yangha

    2009-01-01

    The aim of this study was to investigate the antiobesity effect of (-)-epigallocatechin-3-gallate (EGCG) in diet-induced obese mice. Male C57BL/6J mice were fed on a high-fat diet for 8 weeks to induce obesity. Subsequently they were divided into 3 groups and were maintained on a high-fat control diet or high-fat diets supplemented with 0.2 or 0.5% EGCG (w/w) for a further 8 weeks. Changes in the expression of genes related to lipid metabolism and fatty acid oxidation were analyzed in white adipose tissue, together with biometric and blood parameters. Experimental diets supplemented with EGCG resulted in reduction of body weight and mass of various adipose tissues in a dose-dependent manner. EGCG diet also considerably lowered the levels of plasma triglyceride and liver lipid. In the epididymal white adipose tissue of EGCG diet-fed mice, the mRNA levels of adipogenic genes such as peroxisome proliferator-activated receptor-gamma (PPAR-gamma), CCAAT enhancer-binding protein-alpha (C/EBP-alpha), regulatory element-binding protein-1c (SREBP-1c), adipocyte fatty acid-binding protein (aP2), lipoprotein lipase (LPL) and fatty acid synthase (FAS) were significantly decreased. However, the mRNA levels of carnitine palmitoyl transferase-1 (CPT-1) and uncoupling protein 2 (UCP2), as well as lipolytic genes such as hormone sensitive lipase (HSL) and adipose triglyceride lipase (ATGL), were significantly increased. These results suggest that green tea EGCG effectively reduces adipose tissue mass and ameliorates plasma lipid profiles in high-fat diet-induced obese mice. These effects might be at least partially mediated via regulation of the expression of multiple genes involved in adipogenesis, lipolysis, beta-oxidation and thermogenesis in white adipose tissue. 2009 S. Karger AG, Basel.

  9. 生长动物脂肪代谢关键酶基因表达调控%Modulating the Expression of Genes Regulating Key Enzymes for Lipid Metabolism in Growing Animals

    Institute of Scientific and Technical Information of China (English)

    岳颖; 刘国华; 郑爱娟; 张华; 王晓方; 李婷婷; 卢占军

    2012-01-01

    动物体内脂肪组织合成与分解代谢的调控主要是通过调控脂肪代谢关键酶的含量和活性来进行的.关键酶的基因表达水平决定了酶蛋白的多寡和活性的高低.本文对脂肪代谢中的脂肪酸合成酶(FAS)、乙酰辅酶A羧化酶(ACC)、激素敏感酯酶(HSL)、脂蛋白酯酶(LPL)的活性及其相应的基因表达水平影响脂肪代谢的研究进展进行综述.%Synthesis and catabolism in animal adipose tissue are mainly regulated by key enzymes of lipid metabolism. Gene expression level determines the amount of enzymes and their activities. This- article mainly reviews the progress in effects of gene expression of some key enzymes (fatty acid synthetase, acetylcoenzyme A, hormone-sensitive lipase and lipoproteinesterase) and their activities on lipid metabolism. [ Chinese Journal of Animal Nutrition, 2012, 24(2) : 232-238

  10. A Novel Mathematical Approach to Define the Genes/SNPs Conferring Risk or Protection in Sporadic Amyotrophic Lateral Sclerosis Based on Auto Contractive Map Neural Networks and Graph Theory

    Directory of Open Access Journals (Sweden)

    Massimo Buscema

    2012-01-01

    Full Text Available Background. Complex diseases like amyotrophic lateral sclerosis (ALS implicate phenotypic and genetic heterogeneity. Therefore, multiple genetic traits may show differential association with the disease. The Auto Contractive Map (AutoCM, belonging to the Artificial Neural Network (ANN architecture, “spatializes” the correlation among variables by constructing a suitable embedding space where a visually transparent and cognitively natural notion such as “closeness” among variables reflects accurately their associations. Results. In this pilot case-control study single nucleotide polymorphism (SNP in several genes has been evaluated with a novel data mining approach based on an AutoCM. We have divided the ALS dataset into two dataset: Cases and Control dataset; we have applied to each one, independently, the AutoCM algorithm. Six genetic variants were identified which differently contributed to the complexity of the system: three of the above genes/SNPs represent protective factors, APOA4, NOS3, and LPL, since their contribution to the whole complexity resulted to be as high as 0.17. On the other hand ADRB3, LIPC, and MMP3, whose hub relevancies contribution resulted to be as high as 0.13, seem to represent susceptibility factors. Conclusion. The biological information available on these six polymorphisms is consistent with possible pathogenetic pathways related to ALS.

  11. Iron Dextran Increases Hepatic Oxidative Stress and Alters Expression of Genes Related to Lipid Metabolism Contributing to Hyperlipidaemia in Murine Model

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    Maísa Silva

    2015-01-01

    Full Text Available The objective of this study was to investigate the effects of iron dextran on lipid metabolism and to determine the involvement of oxidative stress. Fischer rats were divided into two groups: the standard group (S, which was fed the AIN-93M diet, and the standard plus iron group (SI, which was fed the same diet but also received iron dextran injections. Serum cholesterol and triacylglycerol levels were higher in the SI group than in the S group. Iron dextran was associated with decreased mRNA levels of pparα, and its downstream gene cpt1a, which is involved in lipid oxidation. Iron dextran also increased mRNA levels of apoB-100, MTP, and L-FABP indicating alterations in lipid secretion. Carbonyl protein and TBARS were consistently higher in the liver of the iron-treated rats. Moreover, a significant positive correlation was found between oxidative stress products, lfabp expression, and iron stores. In addition, a negative correlation was found between pparα expression, TBARS, carbonyl protein, and iron stores. In conclusion, our results suggest that the increase observed in the transport of lipids in the bloodstream and the decreased fatty acid oxidation in rats, which was promoted by iron dextran, might be attributed to increased oxidative stress.

  12. Expression profiling analysis: Uncoupling protein 2 deficiency improves hepatic glucose, lipid profiles and insulin sensitivity in high-fat diet-fed mice by modulating expression of genes in peroxisome proliferator-activated receptor signaling pathway.

    Science.gov (United States)

    Zhou, Mei-Cen; Yu, Ping; Sun, Qi; Li, Yu-Xiu

    2016-03-01

    Uncoupling protein 2 (UCP2), which was an important mitochondrial inner membrane protein associated with glucose and lipid metabolism, widely expresses in all kinds of tissues including hepatocytes. The present study aimed to explore the impact of UCP2 deficiency on glucose and lipid metabolism, insulin sensitivity and its effect on the liver-associated signaling pathway by expression profiling analysis. Four-week-old male UCP2-/- mice and UCP2+/+ mice were randomly assigned to four groups: UCP2-/- on a high-fat diet, UCP2-/- on a normal chow diet, UCP2+/+ on a high-fat diet and UCP2+/+ on a normal chow diet. The differentially expressed genes in the four groups on the 16th week were identified by Affymetrix gene array. The results of intraperitoneal glucose tolerance test and insulin tolerance showed that blood glucose and β-cell function were improved in the UCP2-/- group on high-fat diet. Enhanced insulin sensitivity was observed in the UCP2-/- group. The differentially expressed genes were mapped to 23 pathways (P signaling pathway' (P = 3.19 × 10(-11)), because it is closely associated with the regulation of glucose and lipid profiles. In the PPAR signaling pathway, seven genes (PPARγ, Dbi, Acsl3, Lpl, Me1, Scd1, Fads2) in the UCP2-/- mice were significantly upregulated. The present study used gene arrays to show that activity of the PPAR signaling pathway involved in the improvement of glucose and lipid metabolism in the liver of UCP2-deficient mice on a long-term high-fat diet. The upregulation of genes in the PPAR signaling pathway could explain our finding that UCP2 deficiency ameliorated insulin sensitivity. The manipulation of UCP2 protein expression could represent a new strategy for the prevention and treatment of diabetes.

  13. Endothelial Genes

    Science.gov (United States)

    2005-06-01

    8217Department of Surgery, Division of Oncology , and 2Department of BRCA-l and BRCA-2 (breast cancer susceptibility genes), Pathology, University of...Suppression subtractive hybridization re- Cancer: principles and practice of oncology . Philadelphia: Lippincott- vealed an RNA sequence (GenBank accession...Lippman ME. Cancer of the breast: molecular biology angiogenesis in sarcomas and carcinomas. Clin Cancer Res 1999;5: of breast cancer. In: DeVita VT

  14. Gene Ontology

    Directory of Open Access Journals (Sweden)

    Gaston K. Mazandu

    2012-01-01

    Full Text Available The wide coverage and biological relevance of the Gene Ontology (GO, confirmed through its successful use in protein function prediction, have led to the growth in its popularity. In order to exploit the extent of biological knowledge that GO offers in describing genes or groups of genes, there is a need for an efficient, scalable similarity measure for GO terms and GO-annotated proteins. While several GO similarity measures exist, none adequately addresses all issues surrounding the design and usage of the ontology. We introduce a new metric for measuring the distance between two GO terms using the intrinsic topology of the GO-DAG, thus enabling the measurement of functional similarities between proteins based on their GO annotations. We assess the performance of this metric using a ROC analysis on human protein-protein interaction datasets and correlation coefficient analysis on the selected set of protein pairs from the CESSM online tool. This metric achieves good performance compared to the existing annotation-based GO measures. We used this new metric to assess functional similarity between orthologues, and show that it is effective at determining whether orthologues are annotated with similar functions and identifying cases where annotation is inconsistent between orthologues.

  15. Influence of Lipid Transport System Gene Polymorphism on the Dyslipidemia and Coronary Lesions in Patients with Unstable Angina

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    Aziz S. Eshpulatov

    2015-12-01

    Full Text Available The purpose of this study was to identify the features of lipid metabolism and coronary lesions in view of the combined carrier of the ε4 allele of APOE ε2/ε3/ε4 polymorphism and the S2 allele of APOC3SstI polymorphism in UA patients. Materials and Methods: The study included 141 Uzbek patients with UA class IIB (Braunwald E. et al., 1989 who had coronary atherosclerosis of varying degrees, according to coronary angiography. The control group consisted of 50 healthy, age-matched, randomly selected Uzbek persons without clinical and instrumental signs of CHD according to the exercise test. Coronary angiography was performed using Allura CV-20 (Philips, Netherlands. Genotyping of the APOE (ε2/ε3/ε4 gene polymorphism and the APOC3 (SstI gene polymorphism was performed by the PCR-RFLP method. Results: Our analysis revealed a significant prevalence of carriers of the S2 allele of APOC3SstI polymorphism and carriers of the ε4 allele of APOE ε2/ε3/ε4 polymorphism among UA patients compared to healthy ethnic Uzbeks. A combination of these two “damaging” alleles was observed in 26.2% of UA patients, which was accompanied by significantly higher blood levels of TC and LDL-C (P<0.05, a higher APOB/APOAI ratio (P<0.05, and a lower level of HDL-C (P<0.05. According to coronary angiography, a three-vessel lesion and more significantly predominated among these UA patients (OR: 2.25, 95% CI: 1.05-4.84, χ2=3.66, p<0.05.

  16. Conservation of a vitellogenin gene cluster in oviparous vertebrates and identification of its traces in the platypus genome.

    Science.gov (United States)

    Babin, Patrick J

    2008-04-30

    Vitellogenin (Vtg) derivatives are the main egg-yolk proteins in most oviparous animal species, and are, therefore, key players in reproduction and embryo development. Conserved synteny and phylogeny were used to identify a Vtg gene cluster (VGC) that had been evolutionarily conserved in most oviparous vertebrates, encompassing the three linked Vtgs on chicken (Gallus gallus) chromosome 8. Tandem arranged homologs to chicken VtgII and VtgIII were retrieved in similar locations in Xenopus (Xenopus tropicalis) and homologous transcribed inverted genes were found in medaka (Oryzias latipes), stickleback (Gasterosteus aculeatus), pufferfish (Takifugu rubripes), and Tetrahodon (Tetraodon nigroviridis), while zebrafish (Danio rerio) Vtg3 may represent a residual trace of VGC in this genome. Vtgs were not conserved in the paralogous chromosomal segment attributed to a whole-genome duplication event in the ancestor of teleosts, while tandem duplicated forms have survived the recent African clawed frog (Xenopus laevis) tetraploidization. Orthologs to chicken VtgI were found in similar locations in teleost fish, as well as in the platypus (Ornithorhynchus anatinus). Additional Vtg fragments found suggested that VGC had been conserved in this egg-laying mammal. A low ratio of nonsynonymous-to-synonymous substitution values and the paucity of pseudogene features suggest functional platypus Vtg products. Genomic identification of Vtgs, Apob, and Mtp in this genome, together with maximum likelihood and Bayesian inference phylogenetic analyses, support the existence of these three large lipid transfer protein superfamily members at the base of the mammalian lineage. In conclusion, the establishment of a VGC in the vertebrate lineage predates the divergence of ray-finned fish and tetrapods and the shift in reproductive and developmental strategy observed between prototherians and therians may be associated with its loss, as shown by its absence from the genomic resources currently

  17. Lipoprotein lipase variants interact with polyunsaturated fatty acids to modulate obesity traits in Puerto Ricans

    Science.gov (United States)

    Lipoprotein lipase (LPL) is a candidate gene for obesity based on its role in triglyceride hydrolysis and the partitioning of fatty acids towards storage or oxidation. Whether dietary fatty acids modify LPL associated obesity risk is unknown. We examined five single nucleotide polymorphisms (SNPs) (...

  18. Ser447stop mutation in lipoprotein lipase is associated with elevated HDL cholesterol levels in normolipidemic males

    NARCIS (Netherlands)

    Kuivenhoven, J A; Groenemeyer, B E; Boer, J. M.; Reymer, P W; Berghuis, Riteke; Bruin, T; Jansen, Hans; Seidell, J C; Kastelein, J J

    This report describes the association between a frequent mutation in the lipoprotein lipase (LPL) gene and HDL cholesterol levels. It concerns a previously described defect that predicts a premature truncation of the LPL protein (447stop). We determined the frequency of this mutation in three groups

  19. Gene doping: gene delivery for olympic victory

    OpenAIRE

    2012-01-01

    With one recently recommended gene therapy in Europe and a number of other gene therapy treatments now proving effective in clinical trials it is feasible that the same technologies will soon be adopted in the world of sport by unscrupulous athletes and their trainers in so called ‘gene doping’. In this article an overview of the successful gene therapy clinical trials is provided and the potential targets for gene doping are highlighted. Depending on whether a doping gene product is secreted...

  20. The lipoprotein lipase gene in combined hyperlipidemia: evidence of a protective allele depletion

    Directory of Open Access Journals (Sweden)

    Malloy Mary J

    2006-07-01

    Full Text Available Abstract Background Lipoprotein Lipase (LPL, a key enzyme in lipid metabolism, catalyzes the hydrolysis of triglycerides (TG from TG-rich lipoproteins, and serves a bridging function that enhances the cellular uptake of lipoproteins. Abnormalities in LPL function are associated with pathophysiological conditions, including familial combined hyperlipidemia (FCH. Whereas two LPL susceptibility alleles were found to co-segregate in a few FCH kindred, a role for common, protective alleles remains unexplored. The LPL Ser447Stop (S447X allele is associated with anti-atherogenic lipid profiles and a modest reduction in risk for coronary disease. We hypothesize that significant depletion of the 447X allele exists in combined hyperlipidemia cases versus controls. A case-control design was employed. The polymorphism was assessed by restriction assay in 212 cases and 161 controls. Genotypic, allelic, and phenotypic associations were examined. Results We found evidence of significant allelic (447Xcontrol: 0.130 vs. 447Xcase: 0.031, χ2 = 29.085; 1df; p 2 = 26.09; 1df; p Conclusion These findings suggest a role for the S447X polymorphism in combined hyperlipidemia and demonstrate the importance of evaluating both susceptibility and protective genetic risk factors.

  1. Cryptogenic cirrhosis in a patient with familial hypocholesterolemia due to a new truncated form of apolipoprotein B.

    Science.gov (United States)

    Bonnefont-Rousselot, Dominique; Condat, Bertrand; Sassolas, Agnès; Chebel, Sabrina; Bittar, Randa; Federspiel, Marie-Christine; Cazals-Hatem, Dominique; Bruckert, Eric

    2009-01-01

    Familial hypobetalipoproteinemia (FHBL) is an autosomal codominantly inherited disorder of lipoprotein metabolism characterized by decreased concentrations of low-density lipoprotein-cholesterol and of apolipoprotein B (apoB). Mutations of APOB gene lead to the formation of truncated forms of apoB. The study aimed at determining the truncated form of apoB responsible for FHBL associated with liver cirrhosis in a 27-year-old man. Analysis of the patient's lipoproteins has been performed by SDS-PAGE electrophoresis followed by immunoblotting with monoclonal antibodies. DNA of the family (proband, daughter, wife, father, and mother) was extracted, and PCR amplification was realized; amplicons were screened and sequenced. Electrophoresis allowed us to identify a truncated form of apoB (close to apoB 59%), associated with a new heterozygous apoB variant, 8402 C>G. This mutation creates a stop codon (TAC>TAG, Y2807X) and predicts to generate a truncated protein (apoB-61.9%). No other causes of cirrhosis were established by comprehensive clinical and biological investigations. We described here an unusual clinical observation of a patient with FHBL and early development of liver cirrhosis due to a new truncated form of apoB.

  2. In silico identification and mapping of microsatellite markers on Sus scrofa chromosome 4

    NARCIS (Netherlands)

    Wijk, van H.J.; Liefers, S.C.; Buschbell, H.; Dibbits, B.W.; Harlizius, B.; Groenen, M.A.M.

    2007-01-01

    Apolipoprotein B (APOB) serves an essential role in the assembly and secretion of triglyceride-rich lipoproteins and lipids transport. This study was designed to clone the full-length cDNA of the chicken APOB gene, to characterize the expression profile, and investigate the differential expression

  3. Sort1, encoded by the cardiovascular risk locus 1p13.3, is a regulator of hepatic lipoprotein export

    DEFF Research Database (Denmark)

    Kjølby, Mads Fuglsang; Andersen, Olav Michael; Breiderhoff, Tilman

    2010-01-01

    receptor for apolipoprotein (apo) B100. It interacts with apoB100 in the Golgi and facilitates the formation and hepatic export of apoB100-containing lipoproteins, thereby regulating plasma low-density lipoprotein (LDL) cholesterol. Absence of sortilin in gene-targeted mice reduces secretion...

  4. Developmental Bisphenol A (BPA) Exposure Leads to Sex-specific Modification of Hepatic Gene Expression and Epigenome at Birth that May Exacerbate High-fat Diet-induced Hepatic Steatosis

    Science.gov (United States)

    Strakovsky, Rita S.; Wang, Huan; Engeseth, Nicki J.; Flaws, Jodi A.; Helferich, William G.; Pan, Yuan-Xiang; Lezmi, Stéphane

    2015-01-01

    Developmental bisphenol A (BPA) exposure increases adulthood hepatic steatosis with reduced mitochondrial function. To investigate potential epigenetic mechanisms behind developmental BPA-induced hepatic steatosis, pregnant Sprague-Dawley rats were dosed with vehicle (oil) or BPA (100 μg/kg/day) from gestational day 6 until postnatal day (PND) 21. After weaning, offspring were either challenged with a high-fat (HF; 45% fat) or remained on a control (C) diet until PND110. From PND60 to 90, both BPA and HF diet increased the fat/lean ratio in males only, and the combination of BPA and HF diet appeared to cause the highest ratio. On PND110, Oil-HF, BPA-C, and BPA-HF males had higher hepatic lipid accumulation than Oil-C, with microvesicular steatosis being marked in the BPA-HF group. Furthermore, on PND1, BPA increased and modified hepatic triglycerides (TG) and free fatty acid (FFA) composition in males only. In PND1 males, BPA increased hepatic expression of FFA uptake gene Fat/Cd36, and decreased the expression of TG synthesis- and β-oxidation-related genes (Dgat, Agpat6, Cebpα, Cebpβ, Pck1, Acox1, Cpt1a, Cybb). BPA altered DNA methylation, histone marks (H3Ac, H4Ac, H3Me2K4, H3Me3K36), and decreased the binding of several transcription factors (Pol II, C/EBPβ, SREBP1) within the male Cpt1a gene, the key β-oxidation enzyme. In PND1 females, BPA only increased the expression of genes involved in FFA uptake and TG synthesis (Lpl, Fasn, and Dgat). These data suggest that developmental BPA exposure alters and reprograms hepatic β-oxidation capacity in males, potentially thorough the epigenetic regulation of genes, and further alters the response to a HF diet. PMID:25748669

  5. Daily rhythms of lipid metabolic gene expression in zebra fish liver: Response to light/dark and feeding cycles.

    Science.gov (United States)

    Paredes, J F; López-Olmeda, J F; Martínez, F J; Sánchez-Vázquez, F J

    2015-01-01

    Despite numerous studies about fish nutrition and lipid metabolism, very little is known about the daily rhythm expression of lipogenesis and lipolysis genes. This research aimed to investigate the existence of daily rhythm expressions of the genes involved in lipid metabolism and their synchronization to different light/dark (LD) and feeding cycles in zebra fish liver. For this purpose, three groups of zebra fish were submitted to a 12:12 h LD cycle. A single daily meal was provided to each group at various times: in the middle of the light phase (ML); in the middle of the dark phase (MD); at random times. After 20 days of acclimation to these experimental conditions, liver samples were collected every 4 h in one 24-h cycle. The results revealed that most genes displayed a significant daily rhythm with an acrophase of expression in the dark phase. The acrophase of lipolytic genes (lipoprotein lipase - lpl, peroxisome proliferator-activated receptor - pparα and hydroxyacil CoA dehydrogenase - hadh) was displayed between ZT 02:17 h and ZT 18:31 h. That of lipogenic genes (leptin-a - lepa, peroxisome proliferator-activated receptor - pparγ, liver X receptor - lxr, insulin-like growth factor - igf1, sterol regulatory element-binding protein - srebp and fatty acid synthase - fas) was displayed between ZT 15:25 h and 20:06 h (dark phase). Feeding time barely influenced daily expression rhythms, except for lxr in the MD group, whose acrophase shifted by about 14 h compared with the ML group (ZT 04:31 h versus ZT 18:29 h, respectively). These results evidence a strong synchronization to the LD cycle, but not to feeding time, and most genes showed a nocturnal acrophase. These findings highlight the importance of considering light and feeding time to optimize lipid metabolism and feeding protocols in fish farming.

  6. Identification of differentially expressed ovarian genes during primary and early secondary oocyte growth in coho salmon, Oncorhynchus kisutch

    Directory of Open Access Journals (Sweden)

    Iliev Dimitar B

    2008-01-01

    Full Text Available Abstract Background The aim of this study was to identify differentially expressed ovarian genes during primary and early secondary oocyte growth in coho salmon, a semelparous teleost that exhibits synchronous follicle development. Methods Reciprocal suppression subtractive hybridization (SSH libraries were generated from ovaries with perinucleolus (P or cortical alveolus (CA stage follicles and selected genes were assessed with quantitative PCR (qPCR. An assessment of changes in RNA composition during oocyte growth and its relationship to transcript levels was also conducted. Results SSH revealed several differentially expressed genes during early oogenesis, some which will not likely be utilized until 1–3 years later in salmon. Zona pellucida glycoprotein (zp genes, vitellogenin receptor (vldlr isoforms, cathepsin B (ctsba, cyclin E (ccne, a DnaJ transcript (dnaja2, and a ferritin subunit (fth3 were significantly elevated at the P stage, while a C-type lectin, retinol dehydrogenase (rdh1, and a coatomer protein subunit (cope were upregulated at the CA stage. Putative follicle cell transcripts such as anti-Müllerian hormone (amh, lipoprotein lipase (lpl, apolipoprotein E (apoe, gonadal soma-derived growth factor (gsdf and follicle-stimulating hormone receptor (fshr also increased significantly at the CA stage. The analysis of RNA composition during oocyte growth showed that the total RNA yield and proportion of messenger RNA relative to non-polyadenylated RNAs declined as oogenesis progressed. This influenced apparent transcript levels depending on the type of RNA template used and normalization method. Conclusion In coho salmon, which exhibit a dramatic change in oocyte size and RNA composition during oogenesis, use of messenger RNA as template and normalization of qPCR data to a housekeeping gene, ef1a, yielded results that best reflected transcript abundance within the ovarian follicle. Synthesis of zp transcripts and proteins involved in

  7. Common variants in the genes of triglyceride and HDL-C metabolism lack association with coronary artery disease in the Pakistani subjects.

    Science.gov (United States)

    Shahid, Saleem Ullah; Shabana, N A; Cooper, Jackie A; Rehman, Abdul; Humphries, Steve E

    2017-01-31

    Serum Triglyceride (TG) and High Density Lipoprotein (HDL-C) levels are modifiable coronary artery disease (CAD) risk factors. Polymorphisms in the genes regulating TG and HDL-C levels contribute to the development of CAD. The objective of the current study was to investigate the effect of four such single nucleotide polymorphism (SNPs) in the genes for Lipoprotein Lipase (LPL) (rs328, rs1801177), Apolipoprotein A5 (APOA5) (rs66279) and Cholesteryl ester transfer protein (CETP) (rs708272) on HDL-C and TG levels and to examine the association of these SNPs with CAD risk. A total of 640 subjects (415 cases, 225 controls) were enrolled in the study. The SNPs were genotyped by KASPar allelic discrimination technique. Serum HDL-C and TG were determined by spectrophotometric methods. The population under study was in Hardy Weinberg equilibrium and minor allele of SNP rs1801177 was completely absent in the studied subjects. The SNPs were association with TG and HDL-C levels was checked through regression analysis. For rs328, the effect size of each risk allele on TG and HDL-C (mmol/l) was 0.16(0.08) and -0.11(0.05) respectively. Similarly, the effect size of rs662799 for TG and HDL-C was 0.12(0.06) and -0.13(0.0.3) and that of rs708272 was 0.08(0.04) and 0.1(0.03) respectively. The risk allele frequencies of the SNPs were higher in cases than controls, but the difference was not significant (p > 0.05) and SNPs were not associated with CAD risk (p > 0.05). The combined gene score of four SNPs significantly raised TG and lowered HDL-C but did not increase CAD risk. The studied SNPs were associated with TG and HDL-C levels, but not with CAD in Pakistani population under study.

  8. Spontaneous intra-uterine growth restriction modulates the endocrine status and the developmental expression of genes in porcine fetal and neonatal adipose tissue.

    Science.gov (United States)

    Gondret, Florence; Père, Marie-Christine; Tacher, Sandrine; Daré, Sophie; Trefeu, Christine; Le Huërou-Luron, Isabelle; Louveau, Isabelle

    2013-12-01

    Low birth weight is correlated with low adiposity at birth, a phenotype that influences neonatal survival and later adiposity. A better understanding of events affecting the fetal adipose tissue development and its functionality around birth is thus needed. This study was undertaken to examine the impact of spontaneous intra-uterine growth restriction (IUGR) on circulating concentrations of hormones and nutrients together with the developmental expression patterns of various genes in subcutaneous adipose tissue of pig fetus during the last third of pregnancy and just after birth. At 71 and 112 days post-conception and 2 days postnatal, pairs of same-sex piglets were chosen within litters to have either a medium (MBW) or a low (LBW) weight (n=6 pairs at each stage). The results indicate that IUGR counteracts the temporal fall of DLK1 gene expression in developing adipose tissue across gestation. It also attenuates the time-dependent increase in expression levels of many genes promoting adipocyte differentiation (PPARG, CEBPA) and lipogenesis (LPL, SREBF1, FASN, FABP4). Opposite responses to IUGR were observed for the IGF system, so that IGF1 mRNA levels were lower (Padipose tissue of LBW piglets compared with MBW piglets. The plasma insulin concentration and the mRNA levels of insulin receptor (INSR) and insulin-responsive glucose transporter (GLUT4) in adipose tissue were also greater in LBW piglets at day 2 postnatal. The data indicate that IUGR delays the normal ontogeny of adipose tissue across gestation and affects the insulin and IGF axes around birth.

  9. GeneEd -- A Genetics Educational Resource

    Science.gov (United States)

    ... Javascript on. Feature: Genetics 101 GeneEd — A Genetics Educational Resource Past Issues / Summer 2013 Table of Contents Science ... The Hereditary Material of Life / GeneEd — A Genetics Educational Resource / Using The Genetics Home Reference Website / Understanding the ...

  10. Effects of polyunsaturated fatty acids from plant oils and algae on milk fat yield and composition are associated with mammary lipogenic and SREBF1 gene expression.

    Science.gov (United States)

    Angulo, J; Mahecha, L; Nuernberg, K; Nuernberg, G; Dannenberger, D; Olivera, M; Boutinaud, M; Leroux, C; Albrecht, E; Bernard, L

    2012-12-01

    The main aim of the present study was to examine the effects of long-term supplementing diets with saturated or unprotected polyunsaturated fatty acids from two different plant oils rich in either n-3 or n-6 fatty acids (FAs) plus docosahexaenoic acid (DHA)-rich algae on mammary gene expression and milk fat composition in lactating dairy cows. Gene expression was determined from mammary tissue and milk epithelial cells. Eighteen primiparous German Holstein dairy cows in mid-lactation were randomly assigned into three dietary treatments that consist of silage-based diets supplemented with rumen-stable fractionated palm fat (SAT; 3.1% of the basal diet dry matter, DM), or a mixture of linseed oil (2.7% of the basal diet DM) plus DHA-rich algae (LINA; 0.4% of the basal diet DM) or a mixture of sunflower oil (2.7% of the basal diet DM) plus DHA-rich algae (SUNA; 0.4% of the basal diet DM), for a period of 10 weeks. At the end of the experimental period, the cows were slaughtered and mammary tissues were collected to study the gene expression of lipogenic enzymes. During the last week, the milk yield and composition were determined, and milk was collected for FA measurements and the isolation of milk purified mammary epithelial cells (MECs). Supplementation with plant oils and DHA-rich algae resulted in milk fat depression (MFD; yield and percentage). The secretion of de novo FAs in the milk was reduced, whereas the secretion of trans-10,cis-12-CLA and DHA were increased. These changes in FA secretions were associated in mammary tissue with a joint down-regulation of mammary lipogenic enzyme gene expression (stearoyl-CoA desaturase, SCD1; FA synthase, FASN) and expression of the regulatory element binding transcription factor (SREBF1), whereas no effect was observed on lipoprotein lipase (LPL) and glycerol-3-phosphate acyltransferase 1, mitochondrial (GPAM). A positive relationship between mammary SCD1 and SREBF1 mRNA abundances was observed, suggesting a similar

  11. Fish oil-induced milk fat depression and associated downregulation of mammary lipogenic genes in dairy ewes.

    Science.gov (United States)

    Carreño, D; Hervás, G; Toral, P G; Castro-Carrera, T; Frutos, P

    2016-10-01

    Several studies in dairy cows have shown a relationship between milk fat depression (MFD) and alterations caused in lipogenic gene expression by dietary nutrients. However, information on small ruminants is not only scarce but also inconsistent. Therefore, this experiment was conducted in dairy ewes to study the effect of a diet known to induce MFD on milk fatty acid (FA) composition and mRNA abundance of key candidate genes involved in mammary lipogenesis. Twelve lactating Assaf ewes (on average 63d in milk) were randomly assigned to 2 treatments consisting of a total mixed ration based on alfalfa hay and concentrates (50:50), supplemented with 0 (control) or 17g of fish oil/kg of diet dry matter (FO). Profiles of milk FA and mRNA abundance of candidate genes in biopsied mammary tissue were examined before starting the treatments and after 1 and 4.5wk on the diets. As expected, FO induced MFD and modified milk FA composition. Compared with the control, reductions in milk fat concentration and yield were not detected on d 7, but reached up to 25 and 22%, respectively, on d 30. However, increases in confirmed or putative antilipogenic FA (trans-10,cis-12 and trans-9,cis-11 18:2, cis-9 16:1, cis-11 18:1, and oxo-FA) were already established on the early stage of the treatment and lasted until the end of the feeding period. These changes were accompanied by decreases in the mRNA abundance of genes encoding lipogenic enzymes. The coordinated nature of the downregulation, which tended to affect most studied metabolic pathways, including FA activation (ACSS1), de novo synthesis (ACACA and FASN), uptake and transport (LPL and FABP3), desaturation (SCD1), and esterification (AGAPT6), supports the involvement of a central regulator of milk fat synthesis. In this regard, without ruling out the potential contribution of PPARG, our results suggest that SREBF1 would have a relevant role in the MFD syndrome in sheep fed FO. Among the other studied transcription factors, the

  12. Low density lipoprotein : structure, dynamics, and interactions of apoB-100 with lipids

    NARCIS (Netherlands)

    Murtola, Teemu; Vuorela, Timo A.; Hyvonen, Marja T.; Marrink, Siewert-Jan; Karttunen, Mikko; Vattulainen, Ilpo

    2011-01-01

    Low-density lipoprotein (LDL) transports cholesterol in the bloodstream and plays an important role in the development of cardiovascular diseases, in particular atherosclerosis. Despite its importance to health, the structure of LDL is not known in detail. This is worrying since the lack of LDL's st

  13. The susceptibility gene screening in a Chinese high-altitude pulmonary edema family by whole-exome sequencing.

    Science.gov (United States)

    Yingzhong, Yang; Yaping, Wang; Jin, Xu; Rili, Ge

    2017-02-20

    High-altitude pulmonary edema (HAPE) is one of idiopathic mountain sicknesses that occur in healthy lowlanders when they quickly ascend to altitudes exceeding 2500 m above sea levels within 1-7 days. Growing evidence suggests that genetics plays an important role in the risk of HAPE. In this study, we recruited a Chinese HAPE family and screened genetic variations in the 7 family members (including 6 family members with a medical history of HAPE and the propositus's mother) by whole-exome sequencing. The results showed 18 genetic variations (9 SNVs and 9 Indels) were related to HAPE. Two SNV sites (CFHR4 (p.L85F) and OXER1 (p.R176C)) were predicted to be damaging and alter protein functions by SIFT, PolyPhen-2 and PROVEAN software. The biological function of OXER1 was highly related to the hypoxia-inducible factor pathway. Therefore, those two sites were identified as candidate pathological variations. Moreover, other SNVs (NMB p.S150P, APOB p.I4194T, EIF4ENIF1 p.Q763P) and Indels (KCNJ12 p.EE333-334E, ANKRD31 p.LMN251-253LN, OR2A14 p.HFFC175-178HFC) were also predicted to be damaging as well, which also might be considered as potential candidate pathological variations related to HAPE. Collectively we firstly screened the susceptibility genes in a Chinese HAPE family by whole-exome sequencing, which will provide new clues for further mechanistic studies of HAPE.

  14. EFFECT OF POMEGRANATE ELLAGIC ACID (PEA) ON THE EXPRESSION OF LIPOGENESIS AND LIPOLYSIS GENES IN HYPERLIPIDEMIC HAMSTERS%石榴鞣花酸对高脂血仓鼠肝脏脂质合成与分解基因表达的影响

    Institute of Scientific and Technical Information of China (English)

    刘润; 李建科; 程玉江; 王丽芳; 霍天博; 薛佳宜

    2015-01-01

    目的:观察石榴鞣花酸(PEA)对饮食诱导性高脂仓鼠脂质合成与分解相关基因的影响,探讨PEA降脂的作用机制。方法采用HPLC法测定PEA主要成分;54只雄性仓鼠随机均分为6组:正常对照组(NG,8w普通饲料);五个高脂组(HFG):模型对照组(MG)、药物对照组(辛伐他汀1.77mg/kg bw ,SG)、PEA低(PEA-L 44 mg/kg bw)、中(PEA-M 88 mg/kg bw)、高(PEA-H 177 mg/kg bw;)剂量组,后5组为前4w高脂饲料,后4w普通饲料;4w高脂模型建立成功后,以灌胃方式连续给予仓鼠对应处理,第4w、8w检测仓鼠血清 TC、TG含量;采用 RT-PCR法测定肝脏中脂质代谢调控因子固醇调节元件结合蛋白-1c(SREBP-1c)mRNA表达和脂肪酸合成酶(FAS)以及脂蛋白脂肪酶(LPL)mRNA表达量。结论 PEA可以降低血液中TC、TG的含量,升高HDL-C的含量,主要通过抑制SREBP-1c mRNA、FAS mRNA的基因表达,促进LPL mRNA的基因表达实现降脂功能。PEA降脂效果存在剂量依赖关系,高剂量PEA 效果较好。%Objective The study was aimed to further investigate the effects of pomegranates ellagic acid (PEA) on lipid metabolism and relevant gene expressions in hyperlipidemic hamster.Method 54 male hamsters were randomly divided into six groups of equal size: normal group (NG), model group (MG), simvastatin group (SG) with 1.77mg/kg simvastatin, PEA low group (PEA-L) with PEA 44 mg/kg, PEA medium group (PEA-M) with PEA 88 mg/kg, PEA high group (PEA-H) with PEA 177 mg/kg. The last 4 groups were treated with simvastatin or PEA for 4 weeks after 4 weeks, respectively. Except NG was given normal diet, other 5 groups were fed a high fat diet at the first 4 weeks and switched to normal diet for the next 4 weeks. At the end of weeks 4 and 8, plasma total cholesterol (TC), triglyceride (TG) and high-density lipoprotein cholesterol (HDL-C) were detected by kits. Real time PCR was used to analyze the mRNA expression of

  15. Special Issue: Gene Conversion in Duplicated Genes

    Directory of Open Access Journals (Sweden)

    Hideki Innan

    2011-06-01

    Full Text Available Gene conversion is an outcome of recombination, causing non-reciprocal transfer of a DNA fragment. Several decades later than the discovery of crossing over, gene conversion was first recognized in fungi when non-Mendelian allelic distortion was observed. Gene conversion occurs when a double-strand break is repaired by using homologous sequences in the genome. In meiosis, there is a strong preference to use the orthologous region (allelic gene conversion, which causes non-Mendelian allelic distortion, but paralogous or duplicated regions can also be used for the repair (inter-locus gene conversion, also referred to as non-allelic and ectopic gene conversion. The focus of this special issue is the latter, interlocus gene conversion; the rate is lower than allelic gene conversion but it has more impact on phenotype because more drastic changes in DNA sequence are involved.

  16. Molecular cloning, expression pattern analysis of porcine Rb1 gene and its regulatory roles during primary dedifferentiated fat cells adipogenic differentiation.

    Science.gov (United States)

    Hu, Xiaoming; Luo, Pei; Peng, Xuewu; Song, Tongxing; Zhou, Yuanfei; Wei, Hongkui; Peng, Jian; Jiang, Siwen

    2015-04-01

    Adipocytes are the main constituent of adipose tissue and are considered to be a corner stone in the homeostatic control of whole body metabolism. Recent reports evidenced that retinoblastoma 1 (Rb1) gene plays an important role in fat development and adipogenesis in mice. Here, we cloned the partial cDNA sequences of the porcine Rb1 gene which contains the complete coding sequences (CDS) of 2820bp encoding a protein of 939 amino acids. Bioinformatic analysis revealed that the CDS of porcine Rb1 was highly identical with those of cattle, human and mice. The porcine Rb1 has three typical conserved structural domains, including Rb-A pocket domain, CYCLIN domain and C-terminus domain, and the phylogenetic tree indicates a closer genetic relationship with cattle and human. Tissue distribution analysis showed that Rb1 expression appeared to be ubiquitously in various tissues, being higher in heart, liver, muscle, and stomach. Furthermore, significant downregulation of Rb1 was found at the initial stage of dedifferentiated fat (DFAT) cells adipogenic differentiation. With the knockdown of the Rb1 expression by siRNA, the number of DFAT cells recruited to white rather than brown adipogenesis was promoted, and mRNA levels of adipogenic markers, such as PPARγ, aP2, LPL and adiponectin and protein expression of PPARγ and adiponectin were increased after hormone stimulation. The underlying mechanisms may be that knockdown of Rb1 promotes the mitotic clonal expansion and PPARγ expression by derepressing the transcriptional activity of E2F so as to facilitate the first steps of adipogenesis. In summary, we cloned and characterized an important negative regulator in adipogenic commitment of porcine DFAT cells.

  17. A genome-wide association and gene-environment interaction study for serum triglycerides levels in a healthy Chinese male population.

    Science.gov (United States)

    Tan, Aihua; Sun, Jielin; Xia, Ning; Qin, Xue; Hu, Yanling; Zhang, Shijun; Tao, Sha; Gao, Yong; Yang, Xiaobo; Zhang, Haiying; Kim, Seong-Tae; Peng, Tao; Lin, Xiaoling; Li, Li; Mo, Linjian; Liang, Zhengjia; Shi, Deyi; Huang, Zhang; Huang, Xianghua; Liu, Ming; Ding, Qiang; Trent, Jeffrey M; Zheng, S Lilly; Mo, Zengnan; Xu, Jianfeng

    2012-04-01

    Triglyceride (TG) is a complex phenotype influenced by both genetic and environmental factors. Recent genome-wide association studies (GWAS) have identified genes or loci affecting lipid levels; however, such studies in Chinese populations are limited. A two-stage GWAS were conducted to identify genetic variants that were associated with TG in a Chinese population of 3495 men. Gene-environment interactions on serum TG levels were further investigated for the seven single nucleotide polymorphisms (SNPs) that were studied in both stages. Two previously reported SNPs (rs651821 in APOA5, rs328 in LPL) were replicated in the second stage, and the combined P-values were 9.19 × 10(-26) and 1.41 × 10(-9) for rs651821 and rs328, respectively. More importantly, a significant interaction between aldehyde dehydrogenase 2 (ALDH2) rs671 and alcohol consumption on serum TG levels were observed (P = 3.34 × 10(-5)). Rs671 was significantly associated with serum TG levels in drinkers (P = 1.90 × 10(-10)), while no association was observed in non-drinkers (P > 0.05). For drinkers, men carrying the AA/AG genotype have significantly lower serum TG levels, compared with men carrying the GG genotype. For men with the GG genotype, the serum TG levels increased with the quantity of alcohol intake (P = 1.28 × 10(-8) for trend test). We identified a novel, significant interaction effect between alcohol consumption and the ALDH2 rs671 polymorphism on TG levels, which suggests that the effect of alcohol intake on TG occurs in a two-faceted manner. Just one drink can increase TG level in susceptible individuals who carry the GG genotype, while individuals carrying AA/AG genotypes may actually benefit from moderate drinking.

  18. Principles of gene therapy

    OpenAIRE

    Mammen Biju; Ramakrishnan T; Sudhakar Uma; Vijayalakshmi

    2007-01-01

    Genes are specific sequences of bases that encode instructions to make proteins. When genes are altered so that encoded proteins are unable to carry out their normal functions, genetic disorders can result. Gene therapy is designed to introduce genetic material into cells to compensate for abnormal genes or to make a beneficial protein. This article reviews the fundamentals in gene therapy and its various modes of administration with an insight into the role of gene therapy in Periodontics an...

  19. Polymorphisms at cholesterol 7α-hydroxylase, apolipoproteins B and E and low density lipoprotein receptor genes in patients with gallbladder stone disease

    Institute of Scientific and Technical Information of China (English)

    Zhao-Yan Jiang; Yu Jiang; Sheng-Dao Zhang; Tian-Quan Han; Guang-Jun Suo; Dian-Xu Feng; Sheng Chen; Xing-Xing Cai; Zhi-Hong Jiang; Jun Shang; Yi Zhang

    2004-01-01

    AIM: To investigate the relationship between gallbladder stone disease (GSD) and single nucleotide polymorphisms of cholesterol 7α-hydroxylase (CYP7A) gene promoter,apolipoprotein (4PO) B gene exon 26, 4POEgene exon 4 or microsatellite polymorphism of low density lipoprotein receptor (LDLR) gene exon 18.METHODS: Genotypes of CYP7A, APOB, APOE and LDLR genes were determined in 105 patients with GSD diagnosed by B-mode ultrasonography and 274 control subjects.Serum lipids were analyzed with HITACHI 7060 automaiC biochemical analyzer.RESULTS: Body mass index (BMI) was significantly higher in patients with GSD (24.47±3.09) than in controls (23.50±2.16).Plasma total cholesterol was lower in patients with GSD (4.66±0.92 mmol/L) than in controls (4.91±0.96 mmol/L),P<0.01 after adjusted for age, sex and BMI. The significantly higher frequency of A allele of CYP7,4 gene polymorphism and X+ allele of APOBgene polymorphism was seen in GSD patients. Percentages of A allele in patients and controls were 62.86% and 54.38% (P <0.05) and those of X+ allele 8.57% and 4.01% (P<0.01). Subjects with A allele had significantly lower plasma total cholesterol and LDL cholesterol than subjects with CC homozygote. In a multiple variable logistic regression model, the BMI (OR=1.13, 95% CI: 1.05-1.22), A allele (OR=1.48, 95% CI: 1.05-2.09) and X+ allele (OR=2.28, 95% CI: 1.14-4.59) were positively associated with GSD (P <0.05). Plasma total cholesterol (OR=0.69, 95% CI: 0.64-0.74) was negatively related to SSD (P<0.05).CONCLUSION: With an association analysis, it was determined that A allele of CYP74 gene and X+ allele of 4POBgene might be considered as risk genes for GSD. These alleles are related with differences of serum lipids among subjects.Multiple-variable logistic regression model analysis showed that besides BMI, GSD was affected by polygenetic factors.But the mechanism for these two alleles responsible for GSD requires further investigations.

  20. Organization of immunoglobulin genes.

    Science.gov (United States)

    Tonegawa, S; Brack, C; Hozumi, N; Pirrotta, V

    1978-01-01

    The nucleotide-sequence determination of a cloned, embryonic Vlambda gene directly demonstrated that V genes are separate from a corresponding C gene in embryonic cells. Analysis by restriction enzymes of total cellular DNA from various sources strongly suggested that the two separate immunoglobulin genes become continuous during differentiation of B lymphocytes. There seems to be a strict correlation between the joining event and activation of the joined genes. Cloning of more immunoglobulin genes from embryo and plasma cells will not only provide direct demonstration of such a gene-joining event but also help in the elucidation of a possible relationship of the event to gene activation mechanisms.

  1. Expression of genes controlling fat deposition in two genetically diverse beef cattle breeds fed high or low silage diets

    Science.gov (United States)

    2013-01-01

    Background Both genetic background and finishing system can alter fat deposition, thus indicating their influence on adipogenic and lipogenic factors. However, the molecular mechanisms underlying fat deposition and fatty acid composition in beef cattle are not fully understood. This study aimed to assess the effect of breed and dietary silage level on the expression patterns of key genes controlling lipid metabolism in subcutaneous adipose tissue (SAT) and longissimus lumborum (LL) muscle of cattle. To that purpose, forty bulls from two genetically diverse Portuguese bovine breeds with distinct maturity rates, Alentejana and Barrosã, were selected and fed either low (30% maize silage/70% concentrate) or high silage (70% maize silage/30% concentrate) diets. Results The results suggested that enhanced deposition of fatty acids in the SAT from Barrosã bulls, when compared to Alentejana, could be due to higher expression levels of lipogenesis (SCD and LPL) and β-oxidation (CRAT) related genes. Our results also indicated that SREBF1 expression in the SAT is increased by feeding the low silage diet. Together, these results point out to a higher lipid turnover in the SAT of Barrosã bulls when compared to Alentejana. In turn, lipid deposition in the LL muscle is related to the expression of adipogenic (PPARG and FABP4) and lipogenic (ACACA and SCD) genes. The positive correlation between ACACA expression levels and total lipids, as well trans fatty acids, points to ACACA as a major player in intramuscular deposition in ruminants. Moreover, results reinforce the role of FABP4 in intramuscular fat development and the SAT as the major site for lipid metabolism in ruminants. Conclusions Overall, the results showed that SAT and LL muscle fatty acid composition are mostly dependent on the genetic background. In addition, dietary silage level impacted on muscle lipid metabolism to a greater extent than on that of SAT, as evaluated by gene expression levels of adipogenic and

  2. Gene doping: gene delivery for olympic victory.

    Science.gov (United States)

    Gould, David

    2013-08-01

    With one recently recommended gene therapy in Europe and a number of other gene therapy treatments now proving effective in clinical trials it is feasible that the same technologies will soon be adopted in the world of sport by unscrupulous athletes and their trainers in so called 'gene doping'. In this article an overview of the successful gene therapy clinical trials is provided and the potential targets for gene doping are highlighted. Depending on whether a doping gene product is secreted from the engineered cells or is retained locally to, or inside engineered cells will, to some extent, determine the likelihood of detection. It is clear that effective gene delivery technologies now exist and it is important that detection and prevention plans are in place.

  3. Effects of prepartum 2,4-thiazolidinedione on insulin sensitivity, plasma concentrations of tumor necrosis factor-α and leptin, and adipose tissue gene expression.

    Science.gov (United States)

    Schoenberg, K M; Perfield, K L; Farney, J K; Bradford, B J; Boisclair, Y R; Overton, T R

    2011-11-01

    Administration of peroxisome proliferator-activated receptor gamma (PPARγ) ligands, thiazolidinediones (TZD), to prepartum dairy cattle has been shown to improve dry matter intake and decrease circulating nonesterified fatty acids (NEFA) around the time of calving. The objective of this work was to elucidate mechanisms of TZD action in transition dairy cattle by investigating changes in plasma leptin, tumor necrosis factor-α (TNFα), the revised quantitative insulin sensitivity check index (RQUICKI), and adipose tissue gene expression of leptin, PPARγ, lipoprotein lipase (LPL), and fatty acid synthase (FAS). Multiparous Holstein cows (n=40) were administered 0, 2.0, or 4.0 mg of TZD/kg of body weight (BW) by intrajugular infusion once daily from 21 d before expected parturition until parturition. Plasma samples collected daily from 22 d before expected parturition through 21 d postpartum were analyzed for glucose, NEFA, and insulin. Plasma samples collected on d -14, -3, -1, 1, 3, 7, 14, and 49 relative to parturition were also analyzed for leptin and TNFα. Adipose tissue was collected on d 7 before expected parturition from a subset of cows, and gene expression was examined via quantitative real-time PCR. A tendency for a treatment by time effect on plasma leptin prepartum was observed such that values were similar on d -14 but cows receiving 2.0 mg/kg of BW of TZD tended to have lower circulating leptin as calving approached. Postpartum leptin tended to be increased linearly (2.3, 2.4, and 2.5±0.1 ng/mL for 0, 2.0, and 4.0 mg/kg treatments, respectively) in cows that received TZD prepartum. Plasma TNFα increased linearly (2.6, 3.7, and 4.0±0.1 pg/mL) in response to TZD treatment and decreased through the first week postpartum. Calculation of RQUICKI 1/[log(glucose)+log(insulin)+log(NEFA)] suggested altered insulin sensitivity in cows administered TZD that may depend on day relative to calving. Administration of TZD increased adipose tissue expression of

  4. Differences in lipid distribution and expression of peroxisome proliferator-activated receptor gamma and lipoprotein lipase genes in torafugu and red seabream.

    Science.gov (United States)

    Kaneko, Gen; Yamada, Toshihiro; Han, Yuna; Hirano, Yuki; Khieokhajonkhet, Anurak; Shirakami, Hirohito; Nagasaka, Reiko; Kondo, Hidehiro; Hirono, Ikuo; Ushio, Hideki; Watabe, Shugo

    2013-04-01

    Lipid content is one of the major determinants of the meat quality in fish. However, the mechanisms underlying the species-specific distribution of lipid are still poorly understood. The present study was undertaken to investigate the mechanisms associated with lipid accumulation in two species of fish: torafugu (a puffer fish) and red seabream. The lipid content of liver and carcass were 67.0% and 0.8% for torafugu, respectively, and 8.8% and 7.3% for red seabream, respectively. Visceral adipose tissue was only apparent in the red seabream and accounted for 73.3% of its total lipid content. Oil red O staining confirmed this species-specific lipid distribution, and further demonstrated that the lipid in the skeletal muscle of the red seabream was mainly localized in the myosepta. We subsequently cloned cDNAs from torafugu encoding lipoprotein lipase 1 (LPL1) and LPL2, important enzymes for the uptake of lipids from blood circulation system into various tissues. The relative mRNA levels of peroxisome proliferator-activated receptor gamma (PPARγ) and the LPLs of torafugu were determined by quantitative real-time PCR together with their counterparts in red seabream previously reported. The relative mRNA levels of PPARγ and LPL1 correlated closely to the lipid distribution of both fish, being significantly higher in liver than skeletal muscle in torafugu, whereas the highest in the adipose tissue, followed by liver and skeletal muscle in red seabream. However, the relative mRNA levels of LPL2 were tenfold lower than LPL1 in both species and only correlated to lipid distribution in torafugu, suggesting that LPL2 has only a minor role in lipid accumulation. In situ hybridization revealed that the transcripts of LPL1 co-localized with lipids in the adipocytes located along the myosepta of the skeletal muscle of red seabream. These results suggest that the transcriptional regulation of PPARγ and LPL1 is responsible for the species-specific lipid distribution of torafugu

  5. Expression of human apolipoprotein B and assembly of lipoprotein(a) in transgenic mice

    Energy Technology Data Exchange (ETDEWEB)

    Callow, M.J.; Stoltzfus, L.J.; Rubin, E.M. [Lawrence Berkeley Lab., CA (United States); Lawn, R.M. [Stanford Univ., CA (United States)

    1994-03-15

    The atherogenic macromolecule lipoprotein(a) [Lp(a)] has resisted in vivo analyses partly because it is found in a limited number of experimental animals. Although transgenic mice expressing human apolipoprotein (a) [apo(a)] have previously been described, they failed to assemble Lp(a) particles because of the inability of human apo(a) to associate with mouse apolipoprotein B (apoB). The authors isolated a 90-kilobase P1 phagemid containing the human apoB gene and with this DNA generated 13 lines of transgenic mice of which 11 expressed human apoB. The human apoB transcript was expressed and edited in the liver of the transgenic mice. Plasma concentrations of human apoB, as well as low density lipoprotein (LDL), were related to transgene copy number; the transgenic line with the most copies of human apoB had a >4-fold increase in LDL cholesterol compared with nontransgenics and a lipoprotein profile similar to that of humans. When human apoB and apo(a) transgenic mice were bred together, plasma apo(a) in mice expressing both human proteins was tightly associated with lipoproteins in the LDL density region. These studies demonstrate the successful expression of human apoB and the efficient assembly of Lp(a) in mice.

  6. A sib-pair analysis study of 15 candidate genes in French families with morbid obesity: indication for linkage with islet 1 locus on chromosome 5q.

    Science.gov (United States)

    Clément, K; Dina, C; Basdevant, A; Chastang, N; Pelloux, V; Lahlou, N; Berlan, M; Langin, D; Guy-Grand, B; Froguel, P

    1999-02-01

    As part of an ongoing search for susceptibility genes in obese families, we performed linkage analyses in 101 French families between qualitative and quantitative traits related to morbid obesity and polymorphisms located in or near 15 candidate genes whose products are involved in body weight regulation. These included cholecystokinin A and B receptors (CCK-AR and CCK-BR), glucagon-like peptide 1 receptor (GLP-1R), the LIM/homeodomain islet-1 gene (Isl-1), the caudal-type homeodomain 3 (CDX-3), the uncoupling protein 1 (UCP-1), the beta3-adrenoceptor (beta3-AR), the fatty acid-binding protein 2 (FABP-2), the hormone-sensitive lipase (HSL), the lipoprotein lipase (LPL), the apoprotein-C2 (apo-C2), the insulin receptor substrate-1 (IRS-1), the peroxisome proliferator-activated receptor-gamma (PPAR-gamma), tumor necrosis factor-alpha (TNF-alpha), and the liver carnitine palmitoyltransferase-1 (CPT-1). Phenotypes related to obesity such as BMI, adult life body weight gain, fasting leptin, insulin, fasting glycerol, and free fatty acids were used for nonparametric sib-pair analyses. A weak indication for linkage was obtained between the Isl-1 locus and obesity status defined by a z score over one SD of BMI (n = 226 sib pairs, pi = 0.54 +/- 0.02, P = 0.03). Moreover, a suggestive indication for linkage was found between the Isl-1 locus and BMI and leptin values (P = 0.001 and 0.0003, respectively) and leptin adjusted for BMI (P = 0.0001). Multipoint analyses for leptin trait with Isl-1 and two flanking markers (D5S418 and D5S407) showed that the logarithm of odds (LOD) score is 1.73, coinciding with the Isl-1 locus. Although marginally positive indications for linkage in subgroups of families were found with IRS-1, CPT-1, and HSL loci, our data suggested that these genes are not major contributors to obesity. Whether an obesity susceptibility gene (Isl-1 itself or another nearby gene) lies on chromosome 5q should be determined by further analyses.

  7. Gene Cluster Statistics with Gene Families

    Science.gov (United States)

    Durand, Dannie

    2009-01-01

    Identifying genomic regions that descended from a common ancestor is important for understanding the function and evolution of genomes. In distantly related genomes, clusters of homologous gene pairs are evidence of candidate homologous regions. Demonstrating the statistical significance of such “gene clusters” is an essential component of comparative genomic analyses. However, currently there are no practical statistical tests for gene clusters that model the influence of the number of homologs in each gene family on cluster significance. In this work, we demonstrate empirically that failure to incorporate gene family size in gene cluster statistics results in overestimation of significance, leading to incorrect conclusions. We further present novel analytical methods for estimating gene cluster significance that take gene family size into account. Our methods do not require complete genome data and are suitable for testing individual clusters found in local regions, such as contigs in an unfinished assembly. We consider pairs of regions drawn from the same genome (paralogous clusters), as well as regions drawn from two different genomes (orthologous clusters). Determining cluster significance under general models of gene family size is computationally intractable. By assuming that all gene families are of equal size, we obtain analytical expressions that allow fast approximation of cluster probabilities. We evaluate the accuracy of this approximation by comparing the resulting gene cluster probabilities with cluster probabilities obtained by simulating a realistic, power-law distributed model of gene family size, with parameters inferred from genomic data. Surprisingly, despite the simplicity of the underlying assumption, our method accurately approximates the true cluster probabilities. It slightly overestimates these probabilities, yielding a conservative test. We present additional simulation results indicating the best choice of parameter values for data

  8. Lateral gene transfer, rearrangement, reconciliation

    NARCIS (Netherlands)

    Patterson, M.D.; Szollosi, G.; Daubin, V.; Tannier, E.

    2013-01-01

    Background. Models of ancestral gene order reconstruction have progressively integrated different evolutionary patterns and processes such as unequal gene content, gene duplications, and implicitly sequence evolution via reconciled gene trees. These models have so far ignored lateral gene transfer,

  9. Exercise decreases lipogenic gene expression in adipose tissue and alters adipocyte cellularity during weight regain after weight loss.

    Directory of Open Access Journals (Sweden)

    Erin Danielle Giles

    2016-02-01

    Full Text Available Exercise is a potent strategy to facilitate long-term weight maintenance. In addition to increasing energy expenditure and reducing appetite, exercise also favors the oxidation of dietary fat, which likely helps prevent weight re-gain. It is unclear whether this exercise-induced metabolic shift is due to changes in energy balance, or whether exercise imparts additional adaptations in the periphery that limit the storage and favor the oxidation of dietary fat. To answer this question, adipose tissue lipid metabolism and related gene expression were studied in obese rats following weight loss and during the first day of relapse to obesity. Mature, obese rats were weight-reduced for 2 weeks with or without daily treadmill exercise (EX. Rats were weight maintained for 6 weeks, followed by relapse on: a ad libitum low fat diet (LFD, b ad libitum LFD plus EX, or c a provision of LFD to match the positive energy imbalance of exercised, relapsing animals. 24h retention of dietary- and de novo-derived fat were assessed directly using 14C palmitate/oleate and 3H20, respectively. Exercise decreased the size, but increased the number of adipocytes in both retroperitoneal (RP and subcutaneous (SC adipose depots, and prevented the relapse-induced increase in adipocyte size. Further, exercise decreased the expression of genes involved in lipid uptake (CD36 & LPL, de novo lipogenesis (FAS, ACC1, and triacylglycerol synthesis (MGAT & DGAT in RP adipose during relapse following weight loss. This was consistent with the metabolic data, whereby exercise reduced retention of de novo-derived fat even when controlling for the positive energy imbalance. The decreased trafficking of dietary fat to adipose tissue with exercise was explained by reduced energy intake which attenuated energy imbalance during refeeding. Despite having decreased expression of lipogenic genes, the net retention of de novo-derived lipid was higher in both the RP and SC adipose of exercising

  10. Gene doping in sports.

    Science.gov (United States)

    Unal, Mehmet; Ozer Unal, Durisehvar

    2004-01-01

    Gene or cell doping is defined by the World Anti-Doping Agency (WADA) as "the non-therapeutic use of genes, genetic elements and/or cells that have the capacity to enhance athletic performance". New research in genetics and genomics will be used not only to diagnose and treat disease, but also to attempt to enhance human performance. In recent years, gene therapy has shown progress and positive results that have highlighted the potential misuse of this technology and the debate of 'gene doping'. Gene therapies developed for the treatment of diseases such as anaemia (the gene for erythropoietin), muscular dystrophy (the gene for insulin-like growth factor-1) and peripheral vascular diseases (the gene for vascular endothelial growth factor) are potential doping methods. With progress in gene technology, many other genes with this potential will be discovered. For this reason, it is important to develop timely legal regulations and to research the field of gene doping in order to develop methods of detection. To protect the health of athletes and to ensure equal competitive conditions, the International Olympic Committee, WADA and International Sports Federations have accepted performance-enhancing substances and methods as being doping, and have forbidden them. Nevertheless, the desire to win causes athletes to misuse these drugs and methods. This paper reviews the current status of gene doping and candidate performance enhancement genes, and also the use of gene therapy in sports medicine and ethics of genetic enhancement.

  11. Investigation of variants identified in caucasian genome-wide association studies for plasma high-density lipoprotein cholesterol and triglycerides levels in Mexican dyslipidemic study samples.

    Science.gov (United States)

    Weissglas-Volkov, Daphna; Aguilar-Salinas, Carlos A; Sinsheimer, Janet S; Riba, Laura; Huertas-Vazquez, Adriana; Ordoñez-Sánchez, Maria L; Rodriguez-Guillen, Rosario; Cantor, Rita M; Tusie-Luna, Teresa; Pajukanta, Päivi

    2010-02-01

    Although epidemiological studies have demonstrated an increased predisposition to low high-density lipoprotein cholesterol and high triglyceride levels in the Mexican population, Mexicans have not been included in any of the previously reported genome-wide association studies for lipids. We investigated 6 single-nucleotide polymorphisms associated with triglycerides, 7 with high-density lipoprotein cholesterol, and 1 with both triglycerides and high-density lipoprotein cholesterol in recent Caucasian genome-wide association studies in Mexican familial combined hyperlipidemia families and hypertriglyceridemia case-control study samples. These variants were within or near the genes ABCA1, ANGPTL3, APOA5, APOB, CETP, GALNT2, GCKR, LCAT, LIPC, LPL (2), MMAB-MVK, TRIB1, and XKR6-AMAC1L2. We performed a combined analysis of the family-based and case-control studies (n=2298) using the Z method to combine statistics. Ten of the single-nucleotide polymorphisms were nominally significant and 5 were significant after Bonferroni correction (P=2.20 x 10(-3) to 2.6 x 10(-11)) for the number of tests performed (APOA5, CETP, GCKR, and GALNT2). Interestingly, our strongest signal was obtained for triglycerides with the minor allele of rs964184 (P=2.6 x 10(-11)) in the APOA1/C3/A4/A5 gene cluster region that is significantly more common in Mexicans (27%) than in whites (12%). It is important to confirm whether known loci have a consistent effect across ethnic groups. We show replication of 5 Caucasian genome-wide association studies lipid associations in Mexicans. The remaining loci will require a comprehensive investigation to exclude or verify their significance in Mexicans. We also demonstrate that rs964184 has a large effect (odds ratio, 1.74) and is more frequent in the Mexican population, and thus it may contribute to the high predisposition to dyslipidemias in Mexicans.

  12. Human Gene Therapy: Genes without Frontiers?

    Science.gov (United States)

    Simon, Eric J.

    2002-01-01

    Describes the latest advancements and setbacks in human gene therapy to provide reference material for biology teachers to use in their science classes. Focuses on basic concepts such as recombinant DNA technology, and provides examples of human gene therapy such as severe combined immunodeficiency syndrome, familial hypercholesterolemia, and…

  13. Maternal undernutrition leads to elevated hepatic triglycerides in male rat offspring due to increased expression of lipoprotein lipase.

    Science.gov (United States)

    Zhu, Wei-Fen; Zhu, Jian-Fang; Liang, Li; Shen, Zheng; Wang, Ying-Min

    2016-05-01

    Small for gestational age (SGA) at birth increases the risk of developing metabolic syndrome, which encompasses various symptoms including hypertriglyceridemia. The aim of the present study was to determine whether maternal undernutrition during pregnancy may lead to alterations in hepatic triglyceride content and the gene expression levels of hepatic lipoprotein lipase (LPL) in SGA male offspring. The present study focused on the male offspring in order to prevent confounding factors, such as estrus cycle and hormone profile. Female Sprague Dawley rats were arbitrarily assigned to receive an ad libitum chow diet or 50% food restricted diet from pregnancy day 1 until parturition. Reverse transcription quantitative polymerase chain reaction and western blot analysis were used to measure the gene expression levels of hepatic LPL at day 1 and upon completion of the third week of age. Chromatin immunoprecipitation quantified the binding activity of liver X receptor‑α (LXR‑α) gene to the LXR response elements (LXRE) on LPL promoter and LPL epigenetic characteristics. At 3 weeks of age, SGA male offspring exhibited significantly elevated levels of hepatic triglycerides, which was concomitant with increased expression levels of LPL. Since LPL is regulated by LXR‑α, the expression levels of LXR‑α were detected in appropriate for gestational age and SGA male offspring. Maternal undernutrition during pregnancy led to an increase in the hepatic expression levels of LXR‑α, and enriched binding to the putative LXR response elements in the LPL promoter regions in 3‑week‑old male offspring. In addition, enhanced acetylation of histone H3 [H3 lysine (K)9 and H3K14] was detected surrounding the LPL promoter. The results of the present study indicated that maternal undernutrition during pregnancy may lead to an increase in hepatic triglycerides, via alterations in the transcriptional and epigenetic regulation of the LPL gene.

  14. PPARγ2 Pro12Ala polymorphism is associated with improved lipoprotein lipase functioning in adipose tissue of insulin resistant obese women.

    Science.gov (United States)

    López-Alarcón, Mardia; Rodríguez-Cruz, Maricela; Vital-Reyes, Victor Saúl; Zavala-Ortega, María Isabel; Hinojosa-Cruz, Juan Carlos; Canizales-Quinteros, Samuel; Fernández, José

    2012-12-15

    Lipoprotein lipase (LPL) plays a pivotal role in lipid metabolism, contributes to metabolic disorders related to insulin action and body weight regulation, and is influenced by inflammation. The Pro12Ala polymorphism of the peroxisome proliferator-activated receptor (PPAR)γ2 gene seems to influence LPL functioning, but its role in obesity and insulin resistance status, which usually coexist in the clinical setting, has not been explored. Our aim was to analyze the association of obesity and insulin resistance with adipose LPL activity and expression, and the influence of the PPARγ2 Pro12Ala polymorphism. A cross-sectional study was conducted in 58 reproductive-age women who underwent elective abdominal surgery. Free-fatty acids, glucose, insulin, and selected adipokines were measured in fasting blood samples. DNA was isolated and the polymorphism genotyped. Biopsies of abdominal subcutaneous adipose tissue obtained during surgery were used to determine enzymatic LPL activity and expression; and expression of selected cytokines. Overweight/obese women presented lower LPL activity (P=0.022) and higher circulating TNF-α (P=0.020) than controls. Insulin resistant women also showed borderline lower LPL activity than non-resistant (P=0.052), but adiposity and inflammatory molecules were comparable. Nevertheless, LPL activity was higher in Pro12Ala carriers than in non-carriers after adjusting for obesity, insulin resistance and inflammation. Likewise, adipose LPL expression was increased in carriers while expression of cytokines was decreased. Our data suggest that insulin resistance is associated with low adipose LPL activity independently of obesity, but the PPARγ2 Pro12Ala polymorphism seems to protect the LPL functioning of obese insulin resistant women, likely through regulating inflammation in adipose tissue. Copyright © 2012 Elsevier B.V. All rights reserved.

  15. Birth weight and blood lipid levels in Spanish adolescents: Influence of selected APOE, APOC3 and PPARgamma2 gene polymorphisms. The AVENA Study

    Directory of Open Access Journals (Sweden)

    Fuentes Miguel

    2008-11-01

    Full Text Available Abstract Background There is increasing evidence indicating that genes involved in certain metabolic processes of cardiovascular diseases may be of particular influence in people with low body weight at birth. We examined whether the apolipoprotein (APO E, APOC3 and the peroxisome proliferator-activated receptor-γ-2 (PPARγ2 polymorphisms influence the association between low birth weight and blood lipid levels in healthy adolescents aged 13–18.5 years. Methods A cross-sectional study of 502 Spanish adolescents born at term was conducted. Total (TC and high density lipoprotein cholesterol (HDLc, triglycerides (TG, apolipoprotein (apo A and B, and lipoprotein(a [Lp(a] were measured. Low density lipoprotein cholesterol (LDLc, TC-HDLc, TC/HDLc and apoB/apoA were calculated. Results Low birth weight was associated with higher levels of TC, LDLc, apoB, Lp(a, TC-HDLc, TC/HDLc and apoB/apoA in males with the APOE ε3ε4 genotype, whereas in females, it was associated with lower HDLc and higher TG levels. In males with the APOC3 S1/S2 genotype, low birth weight was associated with lower apoA and higher Lp(a, yet this association was not observed in females. There were no associations between low birth weight and blood lipids in any of the PPARγ2 genotypes. Conclusion The results indicate that low birth weight has a deleterious influence on lipid profile particularly in adolescents with the APOE ε3/ε4 genotype. These findings suggest that intrauterine environment interact with the genetic background affecting the lipid profile in later life.

  16. Genes and Hearing Loss

    Science.gov (United States)

    ... Find an ENT Doctor Near You Genes and Hearing Loss Genes and Hearing Loss Patient Health Information News media interested in covering ... One of the most common birth defects is hearing loss or deafness (congenital), which can affect as many ...

  17. Essential Bacillus subtilis genes

    DEFF Research Database (Denmark)

    Kobayashi, K.; Ehrlich, S.D.; Albertini, A.

    2003-01-01

    To estimate the minimal gene set required to sustain bacterial life in nutritious conditions, we carried out a systematic inactivation of Bacillus subtilis genes. Among approximate to4,100 genes of the organism, only 192 were shown to be indispensable by this or previous work. Another 79 genes were...... predicted to be essential. The vast majority of essential genes were categorized in relatively few domains of cell metabolism, with about half involved in information processing, one-fifth involved in the synthesis of cell envelope and the determination of cell shape and division, and one-tenth related...... to cell energetics. Only 4% of essential genes encode unknown functions. Most essential genes are present throughout a wide range of Bacteria, and almost 70% can also be found in Archaea and Eucarya. However, essential genes related to cell envelope, shape, division, and respiration tend to be lost from...

  18. Cochlear Gene Therapy

    OpenAIRE

    2012-01-01

    The purpose of this review is to highlight recent advances in cochlear gene therapy over the past several years. Cochlear gene therapy has undergone tremendous advances over the past decade. Beginning with some groundbreaking work in 2005 documenting hair cell regeneration using virallymediated delivery of the mouse atonal 1 gene, gene therapy is now being explored as a possible treatment for a variety of causes of hearing loss.

  19. Discovering genes underlying QTL

    Energy Technology Data Exchange (ETDEWEB)

    Vanavichit, Apichart [Kasetsart University, Kamphaengsaen, Nakorn Pathom (Thailand)

    2002-02-01

    A map-based approach has allowed scientists to discover few genes at a time. In addition, the reproductive barrier between cultivated rice and wild relatives has prevented us from utilizing the germ plasm by a map-based approach. Most genetic traits important to agriculture or human diseases are manifested as observable, quantitative phenotypes called Quantitative Trait Loci (QTL). In many instances, the complexity of the phenotype/genotype interaction and the general lack of clearly identifiable gene products render the direct molecular cloning approach ineffective, thus additional strategies like genome mapping are required to identify the QTL in question. Genome mapping requires no prior knowledge of the gene function, but utilizes statistical methods to identify the most likely gene location. To completely characterize genes of interest, the initially mapped region of a gene location will have to be narrowed down to a size that is suitable for cloning and sequencing. Strategies for gene identification within the critical region have to be applied after the sequencing of a potentially large clone or set of clones that contains this gene(s). Tremendous success of positional cloning has been shown for cloning many genes responsible for human diseases, including cystic fibrosis and muscular dystrophy as well as plant disease resistance genes. Genome and QTL mapping, positional cloning: the pre-genomics era, comparative approaches to gene identification, and positional cloning: the genomics era are discussed in the report. (M. Suetake)

  20. Reading and Generalist Genes

    Science.gov (United States)

    Haworth, Claire M. A.; Meaburn, Emma L.; Harlaar, Nicole; Plomin, Robert

    2007-01-01

    Twin-study research suggests that many (but not all) of the same genes contribute to genetic influence on diverse learning abilities and disabilities, a hypothesis called "generalist genes". This generalist genes hypothesis was tested using a set of 10 DNA markers (single nucleotide polymorphisms [SNPs]) found to be associated with early reading…

  1. Journey from Jumping Genes to Gene Therapy.

    Science.gov (United States)

    Whartenby, Katharine A

    2015-01-01

    Gene therapy for cancer is a still evolving approach that resulted from a long history of studies into genetic modification of organisms. The fascination with manipulating gene products has spanned hundreds if not thousands of years, beginning with observations of the hereditary nature of traits in plants and culminating to date in the alteration of genetic makeup in humans via modern technology. From early discoveries noting the potential for natural mobility of genetic material to the culmination of clinical trials in a variety of disease, gene transfer has had an eventful and sometimes tumultuous course. Within the present review is a brief history of the biology of gene transfer, how it came to be applied to genetic diseases, and its early applications to cancer therapies. Some of the different types of methods used to modify cells, the theories behind the approaches, and some of the limitations encountered along the way are reviewed.

  2. Gene conversion in human rearranged immunoglobulin genes.

    Science.gov (United States)

    Darlow, John M; Stott, David I

    2006-07-01

    Over the past 20 years, many DNA sequences have been published suggesting that all or part of the V(H) segment of a rearranged immunoglobulin gene may be replaced in vivo. Two different mechanisms appear to be operating. One of these is very similar to primary V(D)J recombination, involving the RAG proteins acting upon recombination signal sequences, and this has recently been proven to occur. Other sequences, many of which show partial V(H) replacements with no addition of untemplated nucleotides at the V(H)-V(H) joint, have been proposed to occur by an unusual RAG-mediated recombination with the formation of hybrid (coding-to-signal) joints. These appear to occur in cells already undergoing somatic hypermutation in which, some authors are convinced, RAG genes are silenced. We recently proposed that the latter type of V(H) replacement might occur by homologous recombination initiated by the activity of AID (activation-induced cytidine deaminase), which is essential for somatic hypermutation and gene conversion. The latter has been observed in other species, but not in human Ig genes, so far. In this paper, we present a new analysis of sequences published as examples of the second type of rearrangement. This not only shows that AID recognition motifs occur in recombination regions but also that some sequences show replacement of central sections by a sequence from another gene, similar to gene conversion in the immunoglobulin genes of other species. These observations support the proposal that this type of rearrangement is likely to be AID-mediated rather than RAG-mediated and is consistent with gene conversion.

  3. Endogenous apoC-I increases hyperlipidemia in apoE-knockout mice by stimulating VLDL production and inhibiting LPL

    NARCIS (Netherlands)

    Westerterp, M.; Haan, W. de; Berbée, J.F.P.; Havekes, L.M.; Rensen, P.C.N.

    2006-01-01

    Previous studies have shown that overexpression of human apolipoprotein C-I (apoC-I) results in moderate hypercholesterolemia and severe hypertriglyceridemia in mice in the presence and absence of apoE. We assessed whether physiological endogenous apoC-I levels are sufficient to modulate plasma

  4. Gene therapy in periodontics

    Directory of Open Access Journals (Sweden)

    Anirban Chatterjee

    2013-01-01

    Full Text Available GENES are made of DNA - the code of life. They are made up of two types of base pair from different number of hydrogen bonds AT, GC which can be turned into instruction. Everyone inherits genes from their parents and passes them on in turn to their children. Every person′s genes are different, and the changes in sequence determine the inherited differences between each of us. Some changes, usually in a single gene, may cause serious diseases. Gene therapy is ′the use of genes as medicine′. It involves the transfer of a therapeutic or working gene copy into specific cells of an individual in order to repair a faulty gene copy. Thus it may be used to replace a faulty gene, or to introduce a new gene whose function is to cure or to favorably modify the clinical course of a condition. It has a promising era in the field of periodontics. Gene therapy has been used as a mode of tissue engineering in periodontics. The tissue engineering approach reconstructs the natural target tissue by combining four elements namely: Scaffold, signaling molecules, cells and blood supply and thus can help in the reconstruction of damaged periodontium including cementum, gingival, periodontal ligament and bone.

  5. Regulated Gene Therapy.

    Science.gov (United States)

    Breger, Ludivine; Wettergren, Erika Elgstrand; Quintino, Luis; Lundberg, Cecilia

    2016-01-01

    Gene therapy represents a promising approach for the treatment of monogenic and multifactorial neurological disorders. It can be used to replace a missing gene and mutated gene or downregulate a causal gene. Despite the versatility of gene therapy, one of the main limitations lies in the irreversibility of the process: once delivered to target cells, the gene of interest is constitutively expressed and cannot be removed. Therefore, efficient, safe and long-term gene modification requires a system allowing fine control of transgene expression.Different systems have been developed over the past decades to regulate transgene expression after in vivo delivery, either at transcriptional or post-translational levels. The purpose of this chapter is to give an overview on current regulatory system used in the context of gene therapy for neurological disorders. Systems using external regulation of transgenes using antibiotics are commonly used to control either gene expression using tetracycline-controlled transcription or protein levels using destabilizing domain technology. Alternatively, specific promoters of genes that are regulated by disease mechanisms, increasing expression as the disease progresses or decreasing expression as disease regresses, are also examined. Overall, this chapter discusses advantages and drawbacks of current molecular methods for regulated gene therapy in the central nervous system.

  6. Gene therapy: An overview

    Directory of Open Access Journals (Sweden)

    Sudip Indu

    2013-01-01

    Full Text Available Gene therapy "the use of genes as medicine" involves the transfer of a therapeutic or working copy of a gene into specific cells of an individual in order to repair a faulty gene copy. The technique may be used to replace a faulty gene, or to introduce a new gene whose function is to cure or to favorably modify the clinical course of a condition. The objective of gene therapy is to introduce new genetic material into target cells while causing no damage to the surrounding healthy cells and tissues, hence the treatment related morbidity is decreased. The delivery system includes a vector that delivers a therapeutic gene into the patient′s target cell. Functional proteins are created from the therapeutic gene causing the cell to return to a normal stage. The vectors used in gene therapy can be viral and non-viral. Gene therapy, an emerging field of biomedicine, is still at infancy and much research remains to be done before this approach to the treatment of condition will realize its full potential.

  7. Gene therapy in periodontics.

    Science.gov (United States)

    Chatterjee, Anirban; Singh, Nidhi; Saluja, Mini

    2013-03-01

    GENES are made of DNA - the code of life. They are made up of two types of base pair from different number of hydrogen bonds AT, GC which can be turned into instruction. Everyone inherits genes from their parents and passes them on in turn to their children. Every person's genes are different, and the changes in sequence determine the inherited differences between each of us. Some changes, usually in a single gene, may cause serious diseases. Gene therapy is 'the use of genes as medicine'. It involves the transfer of a therapeutic or working gene copy into specific cells of an individual in order to repair a faulty gene copy. Thus it may be used to replace a faulty gene, or to introduce a new gene whose function is to cure or to favorably modify the clinical course of a condition. It has a promising era in the field of periodontics. Gene therapy has been used as a mode of tissue engineering in periodontics. The tissue engineering approach reconstructs the natural target tissue by combining four elements namely: Scaffold, signaling molecules, cells and blood supply and thus can help in the reconstruction of damaged periodontium including cementum, gingival, periodontal ligament and bone.

  8. Cyanobacterial signature genes.

    Science.gov (United States)

    Martin, Kirt A; Siefert, Janet L; Yerrapragada, Sailaja; Lu, Yue; McNeill, Thomas Z; Moreno, Pedro A; Weinstock, George M; Widger, William R; Fox, George E

    2003-01-01

    A comparison of 8 cyanobacterial genomes reveals that there are 181 shared genes that do not have obvious orthologs in other bacteria. These signature genes define aspects of the genotype that are uniquely cyanobacterial. Approximately 25% of these genes have been associated with some function. These signature genes may or may not be involved in photosynthesis but likely they will be in many cases. In addition, several examples of widely conserved gene order involving two or more signature genes were observed. This suggests there may be regulatory processes that have been preserved throughout the long history of the cyanobacterial phenotype. The results presented here will be especially useful because they identify which of the many genes of unassigned function are likely to be of the greatest interest.

  9. Endothelial and lipoprotein lipases in human and mouse placenta

    DEFF Research Database (Denmark)

    Lindegaard, Marie Louise Skakkebæk; Olivecrona, Gunilla; Christoffersen, Christina;

    2005-01-01

    Placenta expresses various lipase activities. However, a detailed characterization of the involved genes and proteins is lacking. In this study, we compared the expression of endothelial lipase (EL) and LPL in human term placenta. When placental protein extracts were separated by heparin...... protein associated with both cell types. In mouse placentas, lack of LPL expression resulted in increased EL mRNA expression. These results suggest that the cellular expression of EL and LPL in human placenta is different. Nevertheless, the two lipases might have overlapping functions in the mouse...... placenta. Our data also suggest that the major portions of both proteins are stored in an inactive form in human term placenta....

  10. Primetime for Learning Genes

    Science.gov (United States)

    Keifer, Joyce

    2017-01-01

    Learning genes in mature neurons are uniquely suited to respond rapidly to specific environmental stimuli. Expression of individual learning genes, therefore, requires regulatory mechanisms that have the flexibility to respond with transcriptional activation or repression to select appropriate physiological and behavioral responses. Among the mechanisms that equip genes to respond adaptively are bivalent domains. These are specific histone modifications localized to gene promoters that are characteristic of both gene activation and repression, and have been studied primarily for developmental genes in embryonic stem cells. In this review, studies of the epigenetic regulation of learning genes in neurons, particularly the brain-derived neurotrophic factor gene (BDNF), by methylation/demethylation and chromatin modifications in the context of learning and memory will be highlighted. Because of the unique function of learning genes in the mature brain, it is proposed that bivalent domains are a characteristic feature of the chromatin landscape surrounding their promoters. This allows them to be “poised” for rapid response to activate or repress gene expression depending on environmental stimuli. PMID:28208656

  11. Primetime for Learning Genes.

    Science.gov (United States)

    Keifer, Joyce

    2017-02-11

    Learning genes in mature neurons are uniquely suited to respond rapidly to specific environmental stimuli. Expression of individual learning genes, therefore, requires regulatory mechanisms that have the flexibility to respond with transcriptional activation or repression to select appropriate physiological and behavioral responses. Among the mechanisms that equip genes to respond adaptively are bivalent domains. These are specific histone modifications localized to gene promoters that are characteristic of both gene activation and repression, and have been studied primarily for developmental genes in embryonic stem cells. In this review, studies of the epigenetic regulation of learning genes in neurons, particularly the brain-derived neurotrophic factor gene (BDNF), by methylation/demethylation and chromatin modifications in the context of learning and memory will be highlighted. Because of the unique function of learning genes in the mature brain, it is proposed that bivalent domains are a characteristic feature of the chromatin landscape surrounding their promoters. This allows them to be "poised" for rapid response to activate or repress gene expression depending on environmental stimuli.

  12. Developmental bisphenol A (BPA) exposure leads to sex-specific modification of hepatic gene expression and epigenome at birth that may exacerbate high-fat diet-induced hepatic steatosis

    Energy Technology Data Exchange (ETDEWEB)

    Strakovsky, Rita S.; Wang, Huan; Engeseth, Nicki J. [Department of Food Science and Human Nutrition, University of Illinois Urbana-Champaign (United States); Flaws, Jodi A. [Department of Comparative Biosciences, University of Illinois Urbana-Champaign (United States); Helferich, William G. [Department of Food Science and Human Nutrition, University of Illinois Urbana-Champaign (United States); Pan, Yuan-Xiang, E-mail: yxpan@illinois.edu [Department of Food Science and Human Nutrition, University of Illinois Urbana-Champaign (United States); Lezmi, Stéphane, E-mail: slezmi@illinois.edu [Department of Pathobiology, University of Illinois Urbana-Champaign (United States)

    2015-04-15

    Developmental bisphenol A (BPA) exposure increases adulthood hepatic steatosis with reduced mitochondrial function. To investigate the potential epigenetic mechanisms behind developmental BPA-induced hepatic steatosis, pregnant Sprague–Dawley rats were dosed with vehicle (oil) or BPA (100 μg/kg/day) from gestational day 6 until postnatal day (PND) 21. After weaning, offspring were either challenged with a high-fat (HF; 45% fat) or remained on a control (C) diet until PND110. From PND60 to 90, both BPA and HF diet increased the fat/lean ratio in males only, and the combination of BPA and HF diet appeared to cause the highest ratio. On PND110, Oil-HF, BPA-C, and BPA-HF males had higher hepatic lipid accumulation than Oil-C, with microvesicular steatosis being marked in the BPA-HF group. Furthermore, on PND1, BPA increased and modified hepatic triglyceride (TG) and free fatty acid (FFA) compositions in males only. In PND1 males, BPA increased hepatic expression of FFA uptake gene Fat/Cd36, and decreased the expression of TG synthesis- and β-oxidation-related genes (Dgat, Agpat6, Cebpα, Cebpβ, Pck1, Acox1, Cpt1a, Cybb). BPA altered DNA methylation and histone marks (H3Ac, H4Ac, H3Me2K4, H3Me3K36), and decreased the binding of several transcription factors (Pol II, C/EBPβ, SREBP1) within the male Cpt1a gene, the key β-oxidation enzyme. In PND1 females, BPA only increased the expression of genes involved in FFA uptake and TG synthesis (Lpl, Fasn, and Dgat). These data suggest that developmental BPA exposure alters and reprograms hepatic β-oxidation capacity in males, potentially through the epigenetic regulation of genes, and further alters the response to a HF diet. - Highlights: • Developmental BPA exposure exacerbates HF-diet induced steatosis in adult males. • Gestational BPA exposure increases hepatic lipid accumulation in neonatal males. • BPA decreases Cpt1a and other hepatic β-oxidation genes in neonatal males. • BPA alters neonatal male Cpt1a

  13. 糖对草鱼肝脂代谢关键基因转录水平的调控研究%Effects of Carbohydrates on Transcription of Five Key Genes Involved in Lipid Metabolism in Hepatopancreas of Grass Carp Ctenopharyngodon idella

    Institute of Scientific and Technical Information of China (English)

    孙君君; 卢荣华; 常志光; 秦超彬; 杨峰; 聂国兴

    2015-01-01

    hepatopancreas of grass carp were in‐vestigated in vivo and in vitro in order to get the exact regulatory mechanisms of carbohydrates on lipid me‐tabolism in grass carp .The expression levels of sterol regulatory element‐binding protein‐1c (SREBP‐1c) , peroxisome proliferator‐activated receptorα(PPARα) and acetyl‐CoA carboxylase (ACC) were analyzed in hepatopancreas of grass carp fed the diets containing low‐carbohydrates (24% ) and high carbohydrates (42% ) using quantitative real‐time fluorescent PCR technology .T he histological observation w as conduc‐ted in hepatopancreas of grass carp fed the diets containing low and high carbohydrates by H‐E staining . The SREBP‐1c ,fatty acid synthase (FAS) and lipoprotein lipase (LPL) gene expression patterns in vitro hepatocytes treated with different concentrations of glucose were detected by the quantitative real‐time flu‐orescent PCR .The results showed that there were significant higher relative expression levels of SREBP‐1c and ACC in the high carbohydrate group than in the control and in low carbohydrate group (P 0 .05) .The histological observation revealed that fat accumu‐lation was induced in the hepatopancreas ,and the expression level of SREBP‐1c ,FAS and LPL was in‐creased first and then decreased with the increasing concentrations of glucose in the hepatocyte cultures , with the maximal level of SREBP‐1c at 10 mmol/L ,and the maximal FAS and LPL at 20 mmol/L in grass carp fed the high carbohydrate diet ( P< 0 .05 ) . T he findings suggested that the expression levels of SREBP‐1c ,FAS ,and LPL were adjusted by dietary glucose ,which may further regulate the transforma‐tion of carbohydrate into fat .T he research data can enrich the glucose metabolism regulation mechanism in fish ,and is expected to provide a theoretical basis for improvement of utilization efficiency of carbohydrates in fish feed .

  14. An Ontology of Gene

    OpenAIRE

    Masuya, Hiroshi; Mizoguchi, Riichiro

    2012-01-01

    The concept of a gene was established in the era of classical genetics and is now essential for life science for elucidating the molecular basis of the coding of genetic information necessary to realize the body of an organism and its biological functions. However, an ontology fully representing multiple aspects of a gene is still not available. In this study, we dissected the biological and ontological definitions of bearers of genetic information, including genes and alleles. Based on this ...

  15. Placental gene therapy

    OpenAIRE

    David, A. L.; Ashcroft, R

    2009-01-01

    Gene therapy uses genetic material as a drug delivery vehicle to express therapeutic proteins. Placental gene therapy may be useful for correction of two important obstetric conditions, foetal growth restriction and pre-eclampsia in which there is a failure of the physiological trophoblast remodelling of the uterine spiral arteries in early pregnancy. The patient in this scenario is the foetus. Placental gene therapy might be justifiable when: there is reasonable certainty that the foetus wil...

  16. Antisense gene silencing

    DEFF Research Database (Denmark)

    Nielsen, Troels T; Nielsen, Jørgen E

    2013-01-01

    Since the first reports that double-stranded RNAs can efficiently silence gene expression in C. elegans, the technology of RNA interference (RNAi) has been intensively exploited as an experimental tool to study gene function. With the subsequent discovery that RNAi could also be applied to mammal......Since the first reports that double-stranded RNAs can efficiently silence gene expression in C. elegans, the technology of RNA interference (RNAi) has been intensively exploited as an experimental tool to study gene function. With the subsequent discovery that RNAi could also be applied...

  17. History of gene therapy.

    Science.gov (United States)

    Wirth, Thomas; Parker, Nigel; Ylä-Herttuala, Seppo

    2013-08-10

    Two decades after the initial gene therapy trials and more than 1700 approved clinical trials worldwide we not only have gained much new information and knowledge regarding gene therapy in general, but also learned to understand the concern that has persisted in society. Despite the setbacks gene therapy has faced, success stories have increasingly emerged. Examples for these are the positive recommendation for a gene therapy product (Glybera) by the EMA for approval in the European Union and the positive trials for the treatment of ADA deficiency, SCID-X1 and adrenoleukodystrophy. Nevertheless, our knowledge continues to grow and during the course of time more safety data has become available that helps us to develop better gene therapy approaches. Also, with the increased understanding of molecular medicine, we have been able to develop more specific and efficient gene transfer vectors which are now producing clinical results. In this review, we will take a historical view and highlight some of the milestones that had an important impact on the development of gene therapy. We will also discuss briefly the safety and ethical aspects of gene therapy and address some concerns that have been connected with gene therapy as an important therapeutic modality.

  18. A complex phenotype in a child with familial HDL deficiency due to a novel frameshift mutation in APOA1 gene (apoA-IGuastalla).

    Science.gov (United States)

    Pisciotta, Livia; Vitali, Cecilia; Favari, Elda; Fossa, Paola; Adorni, Maria Pia; Leone, Daniela; Artom, Nathan; Fresa, Raffaele; Calabresi, Laura; Calandra, Sebastiano; Bertolini, Stefano

    2015-01-01

    We describe a kindred with high-density lipoprotein (HDL) deficiency due to APOA1 gene mutation in which comorbidities affected the phenotypic expression of the disorder. An overweight boy with hypertriglyceridemia (HTG) and HDL deficiency (HDL cholesterol 0.39 mmol/L, apoA-I 40 mg/dL) was investigated. We sequenced the candidate genes for HTG (LPL, APOC2, APOA5, GPIHBP1, LMF1) and HDL deficiency (LCAT, ABCA1 and APOA1), analyzed HDL subpopulations, measured cholesterol efflux capacity (CEC) of sera and constructed a model of the mutant apoA-I. No mutations in HTG-related genes, ABCA1 and LCAT were found. APOA1 sequence showed that the proband, his mother and maternal grandfather were heterozygous of a novel frameshift mutation (c.546_547delGC), which generated a truncated protein (p.[L159Afs*20]) containing 177 amino acids with an abnormal C-terminal tail of 19 amino acids. Trace amounts of this protein were detectable in plasma. Mutation carriers had reduced levels of LpA-I, preβ-HDL and large HDL and no detectable HDL-2 in their plasma; their sera had a reduced CEC specifically the ABCA1-mediated CEC. Metabolic syndrome in the proband explains the extremely low HDL cholesterol level (0.31 mmol/L), which was half of that found in the other carriers. The proband's mother and grandfather, both presenting low plasma low-density lipoprotein cholesterol, were carriers of the β-thalassemic trait, a condition known to be associated with a reduced low-density lipoprotein cholesterol and a reduced prevalence of cardiovascular disease. This trait might have delayed the development of atherosclerosis related to HDL deficiency. In these heterozygotes for apoA-I truncation, the metabolic syndrome has deleterious effect on HDL system, whereas β-thalassemia trait may delay the onset of cardiovascular disease. Copyright © 2015 National Lipid Association. Published by Elsevier Inc. All rights reserved.

  19. Expression of heterologous sigma factors enables functional screening of metagenomic and heterologous genomic libraries.

    Science.gov (United States)

    Gaida, Stefan M; Sandoval, Nicholas R; Nicolaou, Sergios A; Chen, Yili; Venkataramanan, Keerthi P; Papoutsakis, Eleftherios T

    2015-05-06

    A key limitation in using heterologous genomic or metagenomic libraries in functional genomics and genome engineering is the low expression of heterologous genes in screening hosts, such as Escherichia coli. To overcome this limitation, here we generate E. coli strains capable of recognizing heterologous promoters by expressing heterologous sigma factors. Among seven sigma factors tested, RpoD from Lactobacillus plantarum (Lpl) appears to be able of initiating transcription from all sources of DNA. Using the promoter GFP-trap concept, we successfully screen several heterologous and metagenomic DNA libraries, thus enlarging the genomic space that can be functionally sampled in E. coli. For an application, we show that screening fosmid-based Lpl genomic libraries in an E. coli strain with a chromosomally integrated Lpl rpoD enables the identification of Lpl genetic determinants imparting strong ethanol tolerance in E. coli. Transcriptome analysis confirms increased expression of heterologous genes in the engineered strain.

  20. Delivery Systems in Gene Therapy

    Institute of Scientific and Technical Information of China (English)

    Liu Hu; Anas El-Aneed; Cui Guohui

    2005-01-01

    1 Gene therapy Gene therapy includes the treatment of both genetically based and infectious diseases by introducing genetic materials which have therapeutic effects[1~3]. In its simplest terms, a wild type gene (which is non-functional in the cell leading to disease development) is introduced into the somatic cell lacking this gene to restore the normal gene function in this cell. Many gene therapy strategies, however, utilize genes to destroy specific cells.

  1. Gene promoters dictate histone occupancy within genes.

    Science.gov (United States)

    Perales, Roberto; Erickson, Benjamin; Zhang, Lian; Kim, Hyunmin; Valiquett, Elan; Bentley, David

    2013-10-01

    Spt6 is a transcriptional elongation factor and histone chaperone that reassembles transcribed chromatin. Genome-wide H3 mapping showed that Spt6 preferentially maintains nucleosomes within the first 500 bases of genes and helps define nucleosome-depleted regions in 5' and 3' flanking sequences. In Spt6-depleted cells, H3 loss at 5' ends correlates with reduced pol II density suggesting enhanced transcription elongation. Consistent with its 'Suppressor of Ty' (Spt) phenotype, Spt6 inactivation caused localized H3 eviction over 1-2 nucleosomes at 5' ends of Ty elements. H3 displacement differed between genes driven by promoters with 'open'/DPN and 'closed'/OPN chromatin conformations with similar pol II densities. More eviction occurred on genes with 'closed' promoters, associated with 'noisy' transcription. Moreover, swapping of 'open' and 'closed' promoters showed that they can specify distinct downstream patterns of histone eviction/deposition. These observations suggest a novel function for promoters in dictating histone dynamics within genes possibly through effects on transcriptional bursting or elongation rate.

  2. Smart Genes, Stupid Science.

    Science.gov (United States)

    Randerson, Sherman; Mahadeva, Madhu N.

    1983-01-01

    Because many people still believe that specific, identifiable genes dictate the level of human intelligence and that the number/quality of these genes can be evaluated, presents evidence from human genetics (related to nervous system development) to counter this view. Also disputes erroneous assumptions made in "heritability studies" of human…

  3. XLMR genes: update 2000.

    NARCIS (Netherlands)

    Chiurazzi, P.; Hamel, B.C.J.; Neri, G.

    2001-01-01

    This is the sixth edition of the catalogue of XLMR genes, ie X-linked genes whose malfunctioning causes mental retardation. The cloning era is not yet concluded, actually much remains to be done to account for the 202 XLMR conditions listed in this update. Many of these may eventually prove to be du

  4. Glaucoma Genes and Mechanisms.

    Science.gov (United States)

    Wiggs, Janey L

    2015-01-01

    Genetic studies have yielded important genes contributing to both early-onset and adult-onset forms of glaucoma. The proteins encoded by the current collection of glaucoma genes participate in a broad range of cellular processes and biological systems. Approximately half the glaucoma-related genes function in the extracellular matrix, however proteins involved in cytokine signaling, lipid metabolism, membrane biology, regulation of cell division, autophagy, and ocular development also contribute to the disease pathogenesis. While the function of these proteins in health and disease are not completely understood, recent studies are providing insight into underlying disease mechanisms, a critical step toward the development of gene-based therapies. In this review, genes known to cause early-onset glaucoma or contribute to adult-onset glaucoma are organized according to the cell processes or biological systems that are impacted by the function of the disease-related protein product.

  5. A novel missense mutation in the C-terminal domain of lipoprotein lipase (Glu410-->Val) leads to enzyme inactivation and familial chylomicronemia.

    Science.gov (United States)

    Previato, L; Guardamagna, O; Dugi, K A; Ronan, R; Talley, G D; Santamarina-Fojo, S; Brewer, H B

    1994-09-01

    Lipoprotein lipase (LPL) is a complex enzyme consisting of multiple functional domains essential for the initial hydrolysis of triglycerides present in plasma lipoproteins. Previous studies have localized the catalytic domain of LPL, responsible for the hydrolytic function of the enzyme, to the N-terminus whereas the C-terminal end may play a role in lipid and heparin binding. To date, most described missense mutations resulting in a nonfunctional LPL have been located in the N-terminal region of the enzyme. In this manuscript we describe the defect in the LPL gene of a patient with triglycerides ranging from normal to 12,000 mg/dl, low LPL mass, and no LPL activity in post-heparin plasma. Sequencing of patient PCR-amplified DNA identified two separate mutations in the C-terminal domain of LPL: an A-->T transversion at nucleotide 1484 resulting in a Glu410-->Val substitution and a C-->G mutation at position 1595 that introduces a premature stop codon at position 447. Digestion with MaeIII and MnII established that the patient is a true homozygote for both mutations. In order to investigate the functional significance of these defects, mutant enzymes containing either the Val410 or the Ter447 mutations as well as both Val410 and Ter447, were expressed in vitro. Compared to the wild-type enzyme, LPL447 demonstrated a moderate reduction of specific activity using triolein (70% of normal) and tributyrin (74% of normal) substrates, while LPL410 had a significant (11% and 23% of normal) reduction of the normal lipase and esterase specific activities, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

  6. Gene therapy for hemophilia.

    Science.gov (United States)

    Chuah, M K; Evens, H; VandenDriessche, T

    2013-06-01

    Hemophilia A and B are X-linked monogenic disorders resulting from deficiencies of factor VIII and FIX, respectively. Purified clotting factor concentrates are currently intravenously administered to treat hemophilia, but this treatment is non-curative. Therefore, gene-based therapies for hemophilia have been developed to achieve sustained high levels of clotting factor expression to correct the clinical phenotype. Over the past two decades, different types of viral and non-viral gene delivery systems have been explored for hemophilia gene therapy research with a variety of target cells, particularly hepatocytes, hematopoietic stem cells, skeletal muscle cells, and endothelial cells. Lentiviral and adeno-associated virus (AAV)-based vectors are among the most promising vectors for hemophilia gene therapy. In preclinical hemophilia A and B animal models, the bleeding phenotype was corrected with these vectors. Some of these promising preclinical results prompted clinical translation to patients suffering from a severe hemophilic phenotype. These patients receiving gene therapy with AAV vectors showed long-term expression of therapeutic FIX levels, which is a major step forwards in this field. Nevertheless, the levels were insufficient to prevent trauma or injury-induced bleeding episodes. Another challenge that remains is the possible immune destruction of gene-modified cells by effector T cells, which are directed against the AAV vector antigens. It is therefore important to continuously improve the current gene therapy approaches to ultimately establish a real cure for hemophilia. © 2013 International Society on Thrombosis and Haemostasis.

  7. Gene amplification in carcinogenesis

    Directory of Open Access Journals (Sweden)

    Lucimari Bizari

    2006-01-01

    Full Text Available Gene amplification increases the number of genes in a genome and can give rise to karyotype abnormalities called double minutes (DM and homogeneously staining regions (HSR, both of which have been widely observed in human tumors but are also known to play a major role during embryonic development due to the fact that they are responsible for the programmed increase of gene expression. The etiology of gene amplification during carcinogenesis is not yet completely understood but can be considered a result of genetic instability. Gene amplification leads to an increase in protein expression and provides a selective advantage during cell growth. Oncogenes such as CCND1, c-MET, c-MYC, ERBB2, EGFR and MDM2 are amplified in human tumors and can be associated with increased expression of their respective proteins or not. In general, gene amplification is associated with more aggressive tumors, metastases, resistance to chemotherapy and a decrease in the period during which the patient stays free of the disease. This review discusses the major role of gene amplification in the progression of carcinomas, formation of genetic markers and as possible therapeutic targets for the development of drugs for the treatment of some types of tumors.

  8. Antisense gene silencing

    DEFF Research Database (Denmark)

    Nielsen, Troels T; Nielsen, Jørgen E

    2013-01-01

    Since the first reports that double-stranded RNAs can efficiently silence gene expression in C. elegans, the technology of RNA interference (RNAi) has been intensively exploited as an experimental tool to study gene function. With the subsequent discovery that RNAi could also be applied...... to mammalian cells, the technology of RNAi expanded from being a valuable experimental tool to being an applicable method for gene-specific therapeutic regulation, and much effort has been put into further refinement of the technique. This review will focus on how RNAi has developed over the years and how...

  9. Lipoprotein Lipase as a Candidate Target for Cancer Prevention/Therapy

    Directory of Open Access Journals (Sweden)

    Shinji Takasu

    2012-01-01

    Full Text Available Epidemiological studies have shown that serum triglyceride (TG levels are linked with risk of development of cancer, including colorectal and pancreatic cancers, and their precancerous lesions. Thus, it is assumed that serum TG plays an important role in carcinogenesis, and the key enzyme lipoprotein lipase (LPL, which catalyzes the hydrolysis of plasma TG, may therefore be involved. Dysregulation of LPL has been reported to contribute to many human diseases, such as atherosclerosis, chylomicronaemia, obesity, and type 2 diabetes. Recently, it has been reported that LPL gene deficiency, such as due to chromosome 8p22 loss, LPL gene polymorphism, and epigenetic changes in its promoter region gene, increases cancer risk, especially in the prostate. In animal experiments, high serum TG levels seem to promote sporadic/carcinogen-induced genesis of colorectal and pancreatic cancers. Interestingly, tumor suppressive effects of LPL inducers, such as PPAR ligands, NO-1886, and indomethacin, have been demonstrated in animal models. Moreover, recent evidence that LPL plays important roles in inflammation and obesity implies that it is an appropriate general target for chemopreventive and chemotherapeutic agents.

  10. Gene Therapy of Cancerous Diseases

    OpenAIRE

    Valenčáková, A.; Dziaková, A.; Hatalová, E.

    2015-01-01

    Gene therapy of cancerous diseases provides new means of curing patients with oncologic illnesses. There are several approaches in treating cancer by gene therapy. Most commonly used methods are: cancer immunogene therapy, suicide gene therapy, application of tumor-suppressor genes, antiangiogenic therapy, mesenchymal stem cells used as vectors, gene directed enzyme/prodrug therapy and bacteria used as anti-cancer agents. Cancer gene immunotherapy uses several immunologic agents for the purp...

  11. "Bad genes" & criminal responsibility.

    Science.gov (United States)

    González-Tapia, María Isabel; Obsuth, Ingrid

    2015-01-01

    The genetics of the accused is trying to break into the courts. To date several candidate genes have been put forward and their links to antisocial behavior have been examined and documented with some consistency. In this paper, we focus on the so called "warrior gene", or the low-activity allele of the MAOA gene, which has been most consistently related to human behavior and specifically to violence and antisocial behavior. In preparing this paper we had two objectives. First, to summarize and analyze the current scientific evidence, in order to gain an in depth understanding of the state of the issue and determine whether a dominant line of generally accepted scientific knowledge in this field can be asserted. Second, to derive conclusions and put forward recommendations related to the use of genetic information, specifically the presence of the low-activity genotype of the MAOA gene, in modulation of criminal responsibility in European and US courts.

  12. Gene Expression Omnibus (GEO)

    Data.gov (United States)

    U.S. Department of Health & Human Services — Gene Expression Omnibus is a public functional genomics data repository supporting MIAME-compliant submissions of array- and sequence-based data. Tools are provided...

  13. Gene therapy in ophthalmology.

    Science.gov (United States)

    Uthra, Satagopan; Kumaramanickavel, Govindasamy

    2009-09-01

    It has been more than a year since ophthalmologists and scientists under Dr. Robin Ali's team at the Moorsfield Eye Hospital and the Institute of Ophthalmology, University College London, successfully treated patients with a severely blinding disease, Leber's congenital amaurosis (LCA) using gene therapy. This success does not look to be transient, and this achievement in gene replacement therapy clinical trial for LCA has instilled hope in numerous families with patients suffering from this and similar retinal degenerative diseases, for whom restoration of lost vision has remained a distant dream so far. The encouragement that this success has given is expected to also lead to start of clinical trials for other blinding ocular diseases for which gene therapy experiments at the laboratory and animal levels have been successful. This article reviews the various studies that have led to the understanding of gene therapy outcomes in human ocular diseases and attempts to provide a brief sketch of successful clinical trials.

  14. Single nucleotide polymorphisms in obesity-related genes and all-cause and cause-specific mortality: a prospective cohort study

    Directory of Open Access Journals (Sweden)

    Ruczinski Ingo

    2009-10-01

    Full Text Available Abstract Background The aim of this study was to examine the associations between 16 specific single nucleotide polymorphisms (SNPs in 8 obesity-related genes and overall and cause-specific mortality. We also examined the associations between the SNPs and body mass index (BMI and change in BMI over time. Methods Data were analyzed from 9,919 individuals who participated in two large community-based cohort studies conducted in Washington County, Maryland in 1974 (CLUE I and 1989 (CLUE II. DNA from blood collected in 1989 was genotyped for 16 SNPs in 8 obesity-related genes: monoamine oxidase A (MAOA, lipoprotein lipase (LPL, paraoxonase 1 and 2 (PON1 and PON2, leptin receptor (LEPR, tumor necrosis factor-α (TNFα, and peroxisome proliferative activated receptor-γ and -δ (PPARG and PPARD. Data on height and weight in 1989 (CLUE II baseline and at age 21 were collected from participants at the time of blood collection. All participants were followed from 1989 to the date of death or the end of follow-up in 2005. Cox proportional hazards regression was used to obtain the relative risk (RR estimates and 95% confidence intervals (CI for each SNP and mortality outcomes. Results The results showed no patterns of association for the selected SNPs and the all-cause and cause-specific mortality outcomes, although statistically significant associations (p PPARG rs4684847 and all-cause mortality (CC: reference; CT: RR 0.99, 95% CI 0.89, 1.11; TT: RR 0.60, 95% CI 0.39, 0.93 and cancer-related mortality (CC: reference; CT: RR 1.01, 95% CI 0.82, 1.25; TT: RR 0.22, 95% CI 0.06, 0.90 and TNFα rs1799964 and cancer-related mortality (TT: reference; CT: RR 1.23, 95% CI 1.03, 1.47; CC: RR 0.83, 95% CI 0.54, 1.28. Additional analyses showed significant associations between SNPs in LEPR with BMI (rs1137101 and change in BMI over time (rs1045895 and rs1137101. Conclusion Findings from this cohort study suggest that the selected SNPs are not associated with overall

  15. Effects of Selenium-Enriched Probiotics on Lipid Metabolism, Antioxidative Status, Histopathological Lesions, and Related Gene Expression in Mice Fed a High-Fat Diet.

    Science.gov (United States)

    Nido, Sonia Agostinho; Shituleni, Shituleni Andreas; Mengistu, Berhe Mekonnen; Liu, Yunhuan; Khan, Alam Zeb; Gan, Fang; Kumbhar, Shahnawaz; Huang, Kehe

    2016-06-01

    A total of 80 female albino mice were randomly allotted into five groups (n = 16) as follows: (A) normal control, (B) high-fat diet (HFD),; (C) HFD + probiotics (P), (D) HFD + sodium selenite (SS), and (E) HFD + selenium-enriched probiotics (SP). The selenium content of diets in groups A, B, C, D, and E was 0.05, 0.05, 0.05, 0.3, and 0.3 μg/g, respectively. The amount of probiotics contained in groups C and E was similar (Lactobacillus acidophilus 0.25 × 10(11)/mL and Saccharomyces cerevisiae 0.25 × 10(9)/mL colony-forming units (CFU)). The high-fat diet was composed of 15 % lard, 1 % cholesterol, 0.3 % cholic acid, and 83.7 % basal diet. At the end of the 4-week experiment, blood and liver samples were collected for the measurements of lipid metabolism, antioxidative status, histopathological lesions, and related gene expressions. The result shows that HFD significantly increased the body weights and liver damages compared to control, while P, SS, or SP supplementation attenuated the body weights and liver damages in mice. P, SS, or SP supplementation also significantly reversed the changes of alanine aminotransferase (AST), aspartate aminotransferase (ALT), total cholesterol (TC), triglyceride (TG), low-density lipoprotein (LDL), total protein (TP), high-density lipoprotein (HDL), glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), catalasa (CAT), and malondialdehyde (MDA) levels induced by HFD. Generally, adding P, SS, or SP up-regulated mRNA expression of carnitine palmitoyltransferase-I (CPT1), carnitine palmitoyltransferase II (CPT2), acetyl-CoA acetyltransferase II (ACAT2), acyl-coenzyme A oxidase (ACOX2), and peroxisome proliferator-activated receptor alpha (PPARα) and down-regulated mRNA expression of fatty acid synthase (FAS), lipoprotein lipase (LPL), peroxisome proliferator-activated receptor gamma (PPARγ), and sterol regulatory element-binding protein-1 (SREBP1) involved in lipid metabolism. Among the group

  16. Gene therapy for hemophilia.

    Science.gov (United States)

    Hortelano, G; Chang, P L

    2000-01-01

    Hemophilia A and B are X-linked genetic disorders caused by deficiency of the coagulation factors VIII and IX, respectively. Because of the health hazards and costs of current product replacement therapy, much effort is devoted to the development of gene therapy for these disorders. Approaches to gene therapy for the hemophilias include: ex vivo gene therapy in which cells from the intended recipients are explanted, genetically modified to secrete Factor VIII or IX, and reimplanted into the donor; in vivo gene therapy in which Factor VIII or IX encoding vectors are directly injected into the recipient; and non-autologous gene therapy in which universal cell lines engineered to secrete Factor VIII or IX are enclosed in immuno-protective devices before implantation into recipients. Research into these approaches is aided by the many murine and canine models available. While problems of achieving high and sustained levels of factor delivery, and issues related to efficacy, safety and cost are still to be resolved, progress in gene therapy for the hemophilias has been encouraging and is likely to reach human clinical trial in the foreseeable future.

  17. Evidence for homosexuality gene

    Energy Technology Data Exchange (ETDEWEB)

    Pool, R.

    1993-07-16

    A genetic analysis of 40 pairs of homosexual brothers has uncovered a region on the X chromosome that appears to contain a gene or genes for homosexuality. When analyzing the pedigrees of homosexual males, the researcheres found evidence that the trait has a higher likelihood of being passed through maternal genes. This led them to search the X chromosome for genes predisposing to homosexuality. The researchers examined the X chromosomes of pairs of homosexual brothers for regions of DNA that most or all had in common. Of the 40 sets of brothers, 33 shared a set of five markers in the q28 region of the long arm of the X chromosome. The linkage has a LOD score of 4.0, which translates into a 99.5% certainty that there is a gene or genes in this area that predispose males to homosexuality. The chief researcher warns, however, that this one site cannot explain all instances of homosexuality, since there were some cases where the trait seemed to be passed paternally. And even among those brothers where there was no evidence that the trait was passed paternally, seven sets of brothers did not share the Xq28 markers. It seems likely that homosexuality arises from a variety of causes.

  18. Gene-gene, gene-environment, gene-nutrient interactionsand single nucleotide polymorphisms of inflammatorycytokines

    Institute of Scientific and Technical Information of China (English)

    2015-01-01

    Inflammation plays a significant role in the etiologyof type 2 diabetes mellitus (T2DM). The rise in thepro-inflammatory cytokines is the essential step inglucotoxicity and lipotoxicity induced mitochondrialinjury, oxidative stress and beta cell apoptosis inT2DM. Among the recognized markers are interleukin(IL)-6, IL-1, IL-10, IL-18, tissue necrosis factor-alpha(TNF-α), C-reactive protein, resistin, adiponectin, tissueplasminogen activator, fibrinogen and heptoglobins.Diabetes mellitus has firm genetic and very strongenvironmental influence; exhibiting a polygenic modeof inheritance. Many single nucleotide polymorphisms(SNPs) in various genes including those of pro and antiinflammatorycytokines have been reported as a riskfor T2DM. Not all the SNPs have been confirmed byunifying results in different studies and wide variationshave been reported in various ethnic groups. Theinter-ethnic variations can be explained by the factthat gene expression may be regulated by gene-gene,gene-environment and gene-nutrient interactions. Thisreview highlights the impact of these interactions ondetermining the role of single nucleotide polymorphismof IL-6, TNF-α, resistin and adiponectin in pathogenesisof T2DM.

  19. Follicle-stimulating hormone increases the intramuscular fat content and expression of lipid biosynthesis genes in chicken breast muscle

    Institute of Scientific and Technical Information of China (English)

    Xiao-yan CUI; Ying-ying LI; Ran-ran LIU; Gui-ping ZHAO; Mai-qing ZHENG; Qing-he LI; Jie WEN

    2016-01-01

    Intramuscular fat (IMF) is a crucial factor in the quality of chicken meat. The genetic basis underlying it is complex. Folicle-stimulating hormone (FSH), wel-known as an effector in reproductive tissues, was recently discov-ered to stimulate abdominal fat accumulation in chicken. The effect of FSH on IMF accumulation and the underlying molecular regulatory mechanisms controling both IMF and abdominal fat deposition in vivo are largely unknown. In this study, two groups of chickens were treated with chicken FSH or a placebo. The lipid content of breast muscle, abdominal fat volume, and serum concentrations of FSH were examined. Related genes implicated in breast muscle and abdominal fat accumulation were also investigated. Compared to the control group, the triglyceride (TG) content of breast muscle and the percentage of abdominal fat in FSH-treated chickens were significantly increased by 64.9% and 56.5% (P<0.01), respectively. The FSH content in the serum of FSH-treated chickens was 2.1 times than that of control chickens (P<0.01). Results from quantitative real-time polymerase chain reaction (qRT-PCR) assays showed that relative expression levels of fatty acid synthase (FAS), lipoprotein lipase (LPL), diacylglycerol acyltransferase 2 (DGAT2), adipocyte fatty acid binding protein (A-FABP), and peroxisome proliferator-activated receptorγ (PPARγ) were significantly upregulated in breast muscle folowing FSH treatment (P<0.01). Treatment with FSH also signifi-cantly increased relative expression levels ofFAS, LPL, DGAT2, A-FABP, andPPARγ in abdominal fat tissue (P<0.05). The results of principal component analysis (PCA) for gene expression (breast muscle and abdominal fat) showed that the control and FSH treatment groups were well separated, which indicated the reliability of the data. This study demonstrates that FSH plays an important role in IMF accumulation in female chickens, which likely involves the regulation of biosynthesis genes related to lipid

  20. Identification of four soybean reference genes for gene expression normalization

    Science.gov (United States)

    Gene expression analysis requires the use of reference genes stably expressed independently of specific tissues or environmental conditions. Housekeeping genes (e.g., actin, tubulin, ribosomal, polyubiquitin and elongation factor 1-alpha) are commonly used as reference genes with the assumption tha...

  1. The Mycoplasma hominis vaa gene displays a mosaic gene structure

    DEFF Research Database (Denmark)

    Boesen, Thomas; Emmersen, Jeppe M. G.; Jensen, Lise T.;

    1998-01-01

    Mycoplasma hominis contains a variable adherence-associated (vaa) gene. To classify variants of the vaa genes, we examined 42 M. hominis isolated by PCR, DNA sequencing and immunoblotting. This uncovered the existence of five gene categories. Comparison of the gene types revealed a modular compos...

  2. Expression of key lipid metabolism genes in adipose tissue is not altered by once-daily milking during a feed restriction of grazing dairy cows.

    Science.gov (United States)

    Grala, T M; Roche, J R; Phyn, C V C; Rius, A G; Boyle, R H; Snell, R G; Kay, J K

    2013-01-01

    The objective of this study was to investigate the effect of reduced milking frequency, at 2 feeding levels, on gene expression in adipose tissue of grazing dairy cows during early lactation. Multiparous Holstein-Friesian and Holstein-Friesian × Jersey cows (n=120) were grazed on pasture and milked twice daily (2×) from calving to 34±6d in milk (mean ± standard deviation). Cows were then allocated to 1 of 4 treatments in a 2×2 factorial arrangement. Treatments consisted of 2 milking frequencies (2× or once daily; 1×) and 2 feeding levels for 3 wk: adequately fed (AF), consuming 14.3 kg of dry matter/cow per day, or underfed (UF), consuming 8.3 kg of dry matter/cow per day. After the treatment period, all cows were fed to target grazing residuals ≥1,600 kg of DM/cow per day and milked 2× for 20 wk. Adipose tissue was collected from 12 cows per treatment by subcutaneous biopsy at -1, 3, and 5 wk relative to treatment start, RNA was extracted, and transcript abundance of genes involved in lipid metabolism was quantified using a linear mixed model. At the end of the 3-wk treatment period, transcript abundance of genes involved in fatty acid (FA) uptake into adipose tissue (LPL), FA synthesis [FA synthase (FASN) and stearoyl-coenzyme A desaturase (SCD)], FA oxidation [acyl-coenzyme A synthetase long-chain family member 1 (ACSL1) and carnitine palmitoyltransferase 2 (CPT2)], glyceroneogenesis [glycerol-3-phosphate dehydrogenase 1 (GPD1) and pyruvate carboxylase (PC)], and triacylglyceride synthesis [diacylglycerol O-acyltransferase 2 (DGAT2)] were greater in AF1× cows compared with all other treatments. However, when cows were underfed, no effects of milking frequency were observed on transcript abundance of genes involved in adipose lipid metabolism. Despite increases in plasma NEFA concentrations in UF cows, no effects of underfeeding were observed on the transcription of lipolytic genes. At 5 wk, after cows were returned to 2× milking and standard feed

  3. Human placenta secretes apolipoprotein B-100-containing lipoproteins

    DEFF Research Database (Denmark)

    Munk-Madsen, Eva; Lindegaard, Marie Louise Skakkebæk; Andersen, Claus B;

    2004-01-01

    early during pregnancy in the placenta. To examine whether the human placenta produces lipoproteins, we examined apoB and microsomal triglyceride transfer protein (MTP) mRNA expression in placental biopsies. ApoB and MTP are mandatory for assembly and secretion of apoB-containing lipoproteins. Both...... genes were expressed in placenta and microsomal extracts from human placenta contained triglyceride transfer activity, indicating expression of bioactive MTP. To detect lipoprotein secretion, biopsies from term placentas were placed in medium with [(35)S]methionine and [(35)S]cysteine for 3-24 h. Upon...... lipoproteins secreted from placental tissue showed spherical particles with a diameter of 47 +/- 10 nm. These results demonstrate that human placenta expresses both apoB and MTP and consequently synthesize and secrete apoB-100-containing lipoproteins. Placental lipoprotein formation constitutes a novel pathway...

  4. Common and Rare Alleles in Apolipoprotein B Contribute to Plasma Levels of LDL Cholesterol in the General Population

    DEFF Research Database (Denmark)

    Benn, M; Stene, MC; Nordestgaard, BG;

    2008-01-01

    CONTEXT: We have previously shown that rare mutations in the apolipoprotein B gene (APOB) may result in not only severe hypercholesterolemia and ischemic heart disease but also hypocholesterolemia. Despite this, common single-nucleotide polymorphisms (SNPs) in APOB have not convincingly been...... on cholesterol and apolipoprotein B levels. However, as predicted from the magnitude of the observed LDL cholesterol effects, none of these SNPs predicted risk of ischemic heart disease prospectively in the general population, in a case-control study, or as haplotypes. CONCLUSIONS: Multiple common and rare...... demonstrated to affect low-density lipoprotein (LDL) cholesterol levels. OBJECTIVE: We tested the hypothesis that nonsynonymous SNPs in three important functional domains of APOB and APOB tag SNPs predict levels of LDL cholesterol and apolipoprotein B and risk of ischemic heart disease. DESIGN...

  5. Hox genes and study of Hox genes in crustacean

    Institute of Scientific and Technical Information of China (English)

    HOU Lin; CHEN Zhijuan; XU Mingyu; LIN Shengguo; WANG Lu

    2004-01-01

    Homeobox genes have been discovered in many species. These genes are known to play a major role in specifying regional identity along the anterior-posterior axis of animals from a wide range of phyla.The products of the homeotic genes are a set of evolutionarily conserved transcription factors that control elaborate developmental processes and specify cell fates in metazoans. Crustacean, presenting a variety of body plans not encountered in any other class or phylum of the Metazoa, has been shown to possess a single set of homologous Hox genes like insect. The ancestral crustacean Hox gene complex comprised ten genes: eight homologous to the hometic Hox genes and two related to nonhomeotic genes presented within the insect Hox complexes. The crustacean in particular exhibits an abundant diversity segment specialization and tagmosis. This morphological diversity relates to the Hox genes. In crustacean body plan, different Hox genes control different segments and tagmosis.

  6. Entrez Gene: gene-centered information at NCBI

    OpenAIRE

    Maglott, Donna; Ostell, Jim; Pruitt, Kim D; Tatusova, Tatiana

    2006-01-01

    Entrez Gene () is NCBI's database for gene-specific information. Entrez Gene includes records from genomes that have been completely sequenced, that have an active research community to contribute gene-specific information or that are scheduled for intense sequence analysis. The content of Entrez Gene represents the result of both curation and automated integration of data from NCBI's Reference Sequence project (RefSeq), from collaborating model organism databases and from other databases wit...

  7. ApoB and apoM - New aspects of lipoprotein biology in uremia-induced atherosclerosis

    DEFF Research Database (Denmark)

    Christoffersen, Christina; Bartels, Emil D.; Pedersen, Annemarie Aarup

    2017-01-01

    Chronic kidney disease affects as much as 13% of the population, and is associated with a markedly increased risk of developing cardiovascular disease. One of the underlying reasons is accelerated development of atherosclerosis. This can be ascribed both to increased occurrence of traditional car...

  8. Dietary Energy Level Affects Lipid Catabolism-Related Gene Expression in Adipose Tissue of Wujin Pigs%饲粮能量水平对乌金猪脂肪组织脂类分解代谢相关基因表达的影响

    Institute of Scientific and Technical Information of China (English)

    潘洪彬; 王静; 黄英; 赵素梅; 张曦; 葛长荣; 高士争

    2011-01-01

    The aim or this study was to investigate the effects of dietary energy level on the expression of lipid catabolism-related genes in adipose tissue of Wujin pigs. Fifty-four Wujin pigs with body weight of 15 kg were randomly assigned into 3 groups with 3 replicates per group and 6 heads in each replicate. Pigs in low digestive energy group (11. 74 MJ/kg, LDE group) , middle digestive energy group (12.89 MJ/kg, MDE group) and high digestive energy group (14.22 MJ/kg, HDE group) were fed diets with three different digestive energy levels. At the body weight of 30, 60 and 100 kg, pigs were slaughtered and subcutaneous adipose tissue was collected for analysis of gene expression levels of lipid catabolism-related enzymes and factors [ hormone-sensitive lipase ( HSL), carnitine acyl transferase I (CPT-I ), lipoprotein lipase (LPL) and preoxisome prolifer-ator-activated receptor -γ (PPAR-γ) ] by real-time PCR. The results showed as follows: at the body weight of 30 and 100 kg, the gene expression levels of HSL, CPT-I and PPAR-y in adipose tissue of Wujin pigs fed high energy level diet significantly decreased (P <0. 05) , while the gene expression level of LPL significantly increased (P < 0.05); however, at the body weight of 60 kg, the expression levels of the four genes were significantly increased (P <0. 05). The results indicate that high dietary energy level can decrease lipid catabo-lism and fatty acid β-oxadation of Wujin pigs at the body weight of 30 and 100 kg, but enhance lipid catabo-lism and fatty acid β-oxadation of Wujin pigs at the body weight of 60 kg.%本试验旨在研究饲粮不同能量水平对乌金猪脂肪组织脂类分解代谢相关基因表达的影响.选取体重约15 kg的乌金猪54头,随机分为3组,每组3个重复,每个重复6头猪,分别饲喂消化能为11.74(低能组)、12.89(中能组)和14.22 MJ/kg(高能组)的饲粮,在体重30、60和100 kg时屠宰取皮下脂肪组织,提取总RNA,荧光定量PCR法检测脂肪组织

  9. Gene therapy for brain tumors.

    Science.gov (United States)

    Bansal, K; Engelhard, H H

    2000-09-01

    "Gene therapy" can be defined as the transfer of genetic material into a patient's cells for therapeutic purposes. To date, a diverse and creative assortment of treatment strategies utilizing gene therapy have been devised, including gene transfer for modulating the immune system, enzyme prodrug ("suicide gene") therapy, oncolytic therapy, replacement/therapeutic gene transfer, and antisense therapy. For malignant glioma, gene-directed prodrug therapy using the herpes simplex virus thymidine kinase gene was the first gene therapy attempted clinically. A variety of different strategies have now been pursued experimentally and in clinical trials. Although, to date, gene therapy for brain tumors has been found to be reasonably safe, concerns still exist regarding issues related to viral delivery, transduction efficiency, potential pathologic response of the brain, and treatment efficacy. Improved viral vectors are being sought, and potential use of gene therapy in combination with other treatments is being investigated.

  10. Introns in higher plant genes

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    The intron is an important component of eukaryotic gene. Extensive studies have been conducted to get a better understanding of its structure and function. This paper presents a brief review of the structure and function of introns in higher plant genes. It is shown that higher plant introns possess structural properties shared by all eukaryotic introns, however, they also exhibit a striking degree of diversity. The process of intron splicing in higher plant genes involves interaction between multiple cis-acting elements and trans-acting factors, such as 5′ splicing site, 3′ splicing site and many protein factors. The process of intron splicing is an important level at which gene expression is regulated. Especially alternative splicing of intron can regulate time and space of gene expression. In addition, some introns in higher plant genes also regulate gene expression by affecting the pattern of gene expression, enhancing the level of gene expression and driving the gene expression.

  11. Gene therapy prospects--intranasal delivery of therapeutic genes.

    Science.gov (United States)

    Podolska, Karolina; Stachurska, Anna; Hajdukiewicz, Karolina; Małecki, Maciej

    2012-01-01

    Gene therapy is recognized to be a novel method for the treatment of various disorders. Gene therapy strategies involve gene manipulation on broad biological processes responsible for the spreading of diseases. Cancer, monogenic diseases, vascular and infectious diseases are the main targets of gene therapy. In order to obtain valuable experimental and clinical results, sufficient gene transfer methods are required. Therapeutic genes can be administered into target tissues via gene carriers commonly defined as vectors. The retroviral, adenoviral and adeno-associated virus based vectors are most frequently used in the clinic. So far, gene preparations may be administered directly into target organs or by intravenous, intramuscular, intratumor or intranasal injections. It is common knowledge that the number of gene therapy clinical trials has rapidly increased. However, some limitations such as transfection efficiency and stable and long-term gene expression are still not resolved. Consequently, great effort is focused on the evaluation of new strategies of gene delivery. There are many expectations associated with intranasal delivery of gene preparations for the treatment of diseases. Intranasal delivery of therapeutic genes is regarded as one of the most promising forms of pulmonary gene therapy research. Gene therapy based on inhalation of gene preparations offers an alternative way for the treatment of patients suffering from such lung diseases as cystic fibrosis, alpha-1-antitrypsin defect, or cancer. Experimental and first clinical trials based on plasmid vectors or recombinant viruses have revealed that gene preparations can effectively deliver therapeutic or marker genes to the cells of the respiratory tract. The noninvasive intranasal delivery of gene preparations or conventional drugs seems to be very encouraging, although basic scientific research still has to continue.

  12. FunGene: the Functional Gene Pipeline and Repository

    Directory of Open Access Journals (Sweden)

    Jordan A. Fish

    2013-10-01

    Full Text Available Ribosomal RNA genes have become the standard molecular markers for microbial community analysis for good reasons, including universal occurrence in cellular organisms, availability of large databases, and ease of rRNA gene region amplification and analysis. As markers, however, rRNA genes have some significant limitations. The rRNA genes are often present in multiple copies, unlike most protein-coding genes. The slow rate of change in rRNA genes means that multiple species sometimes share identical 16S rRNA gene sequences, while many more species share identical sequences in the short 16S rRNA regions commonly analyzed. In addition, the genes involved in many important processes are not distributed in a phylogenetically coherent manner, potentially due to gene loss or horizontal gene transfer.While rRNA genes remain the most commonly used markers, key genes in ecologically important pathways, e.g., those involved in carbon and nitrogen cycling, can provide important insights into community composition and function not obtainable through rRNA analysis. However, working with ecofunctional gene data requires some tools beyond those required for rRNA analysis. To address this, our Functional Gene Pipeline and Repository (FunGene; http://fungene.cme.msu.edu/ offers databases of many common ecofunctional genes and proteins, as well as integrated tools that allow researchers to browse these collections and choose subsets for further analysis, build phylogenetic trees, test primers and probes for coverage, and download aligned sequences. Additional FunGene tools are specialized to process coding gene amplicon data. For example, FrameBot produces frameshift-corrected protein and DNA sequences from raw reads while finding the most closely related protein reference sequence. These tools can help provide better insight into microbial communities by directly studying key genes involved in important ecological processes.

  13. Gene decay in archaea

    Directory of Open Access Journals (Sweden)

    M. W. J. van Passel

    2007-01-01

    Full Text Available The gene-dense chromosomes of archaea and bacteria were long thought to be devoid of pseudogenes, but with the massive increase in available genome sequences, whole genome comparisons between closely related species have identified mutations that have rendered numerous genes inactive. Comparative analyses of sequenced archaeal genomes revealed numerous pseudogenes, which can constitute up to 8.6% of the annotated coding sequences in some genomes. The largest proportion of pseudogenes is created by gene truncations, followed by frameshift mutations. Within archaeal genomes, large numbers of pseudogenes contain more than one inactivating mutation, suggesting that pseudogenes are deleted from the genome more slowly in archaea than in bacteria. Although archaea seem to retain pseudogenes longer than do bacteria, most archaeal genomes have unique repertoires of pseudogenes.

  14. A review on microcephaly genes

    Directory of Open Access Journals (Sweden)

    Irshad S.

    2012-06-01

    Full Text Available This review aims to summarize the recent findings regarding microcephaly genes. We have discussed the molecular genetics studies of microcephaly genes including a comprehensive appraisal of the seven mapped loci (MCPH1–MCPH7, their corresponding genes and protein products of the genes, their likely role in normal brain development and the details of the mutations reported in these genes.

  15. Gene therapy for skin diseases.

    Science.gov (United States)

    Gorell, Emily; Nguyen, Ngon; Lane, Alfred; Siprashvili, Zurab

    2014-04-01

    The skin possesses qualities that make it desirable for gene therapy, and studies have focused on gene therapy for multiple cutaneous diseases. Gene therapy uses a vector to introduce genetic material into cells to alter gene expression, negating a pathological process. This can be accomplished with a variety of viral vectors or nonviral administrations. Although results are promising, there are several potential pitfalls that must be addressed to improve the safety profile to make gene therapy widely available clinically.

  16. Gene Therapy for Skin Diseases

    OpenAIRE

    2014-01-01

    The skin possesses qualities that make it desirable for gene therapy, and studies have focused on gene therapy for multiple cutaneous diseases. Gene therapy uses a vector to introduce genetic material into cells to alter gene expression, negating a pathological process. This can be accomplished with a variety of viral vectors or nonviral administrations. Although results are promising, there are several potential pitfalls that must be addressed to improve the safety profile to make gene thera...

  17. Correlating Expression Data with Gene Function Using Gene Ontology

    Institute of Scientific and Technical Information of China (English)

    LIU,Qi; DENG,Yong; WANG,Chuan; SHI,Tie-Liu; LI,Yi-Xue

    2006-01-01

    Clustering is perhaps one of the most widely used tools for microarray data analysis. Proposed roles for genes of unknown function are inferred from clusters of genes similarity expressed across many biological conditions.However, whether function annotation by similarity metrics is reliable or not and to what extent the similarity in gene expression patterns is useful for annotation of gene functions, has not been evaluated. This paper made a comprehensive research on the correlation between the similarity of expression data and of gene functions using Gene Ontology. It has been found that although the similarity in expression patterns and the similarity in gene functions are significantly dependent on each other, this association is rather weak. In addition, among the three categories of Gene Ontology, the similarity of expression data is more useful for cellular component annotation than for biological process and molecular function. The results presented are interesting for the gene functions prediction research area.

  18. The gene tree delusion.

    Science.gov (United States)

    Springer, Mark S; Gatesy, John

    2016-01-01

    Higher-level relationships among placental mammals are mostly resolved, but several polytomies remain contentious. Song et al. (2012) claimed to have resolved three of these using shortcut coalescence methods (MP-EST, STAR) and further concluded that these methods, which assume no within-locus recombination, are required to unravel deep-level phylogenetic problems that have stymied concatenation. Here, we reanalyze Song et al.'s (2012) data and leverage these re-analyses to explore key issues in systematics including the recombination ratchet, gene tree stoichiometry, the proportion of gene tree incongruence that results from deep coalescence versus other factors, and simulations that compare the performance of coalescence and concatenation methods in species tree estimation. Song et al. (2012) reported an average locus length of 3.1 kb for the 447 protein-coding genes in their phylogenomic dataset, but the true mean length of these loci (start codon to stop codon) is 139.6 kb. Empirical estimates of recombination breakpoints in primates, coupled with consideration of the recombination ratchet, suggest that individual coalescence genes (c-genes) approach ∼12 bp or less for Song et al.'s (2012) dataset, three to four orders of magnitude shorter than the c-genes reported by these authors. This result has general implications for the application of coalescence methods in species tree estimation. We contend that it is illogical to apply coalescence methods to complete protein-coding sequences. Such analyses amalgamate c-genes with different evolutionary histories (i.e., exons separated by >100,000 bp), distort true gene tree stoichiometry that is required for accurate species tree inference, and contradict the central rationale for applying coalescence methods to difficult phylogenetic problems. In addition, Song et al.'s (2012) dataset of 447 genes includes 21 loci with switched taxonomic names, eight duplicated loci, 26 loci with non-homologous sequences that are

  19. Neighboring Genes Show Correlated Evolution in Gene Expression

    Science.gov (United States)

    Ghanbarian, Avazeh T.; Hurst, Laurence D.

    2015-01-01

    When considering the evolution of a gene’s expression profile, we commonly assume that this is unaffected by its genomic neighborhood. This is, however, in contrast to what we know about the lack of autonomy between neighboring genes in gene expression profiles in extant taxa. Indeed, in all eukaryotic genomes genes of similar expression-profile tend to cluster, reflecting chromatin level dynamics. Does it follow that if a gene increases expression in a particular lineage then the genomic neighbors will also increase in their expression or is gene expression evolution autonomous? To address this here we consider evolution of human gene expression since the human-chimp common ancestor, allowing for both variation in estimation of current expression level and error in Bayesian estimation of the ancestral state. We find that in all tissues and both sexes, the change in gene expression of a focal gene on average predicts the change in gene expression of neighbors. The effect is highly pronounced in the immediate vicinity (genes increasing their expression in humans tend to avoid nuclear lamina domains and be enriched for the gene activator 5-hydroxymethylcytosine, we conclude that, most probably owing to chromatin level control of gene expression, a change in gene expression of one gene likely affects the expression evolution of neighbors, what we term expression piggybacking, an analog of hitchhiking. PMID:25743543

  20. Searching for speciation genes

    DEFF Research Database (Denmark)

    Holt, Benjamin George; Côté, Isabelle M; Emerson, Brent C

    2011-01-01

    Closely related species that show clear phenotypic divergence, but without obvious geographic barriers, can provide opportunities to study how diversification can occur when opportunities for allopatric speciation are limited. We examined genetic divergence in the coral reef fish genus Hypoplectr...... evidence for genes that may be associated with colour morphotype in the genus Hypoplectrus....

  1. Gene therapy in ophthalmology

    Directory of Open Access Journals (Sweden)

    Satagopan Uthra

    2009-01-01

    Full Text Available It has been more than a year since ophthalmologists and scientists under Dr. Robin Ali′s team at the Moorsfield Eye Hospital and the Institute of Ophthalmology, University College London, successfully treated patients with a severely blinding disease, Leber′s congenital amaurosis (LCA using gene therapy. This success does not look to be transient, and this achievement in gene replacement therapy clinical trial for LCA has instilled hope in numerous families with patients suffering from this and similar retinal degenerative diseases, for whom restoration of lost vision has remained a distant dream so far. The encouragement that this success has given is expected to also lead to start of clinical trials for other blinding ocular diseases for which gene therapy experiments at the laboratory and animal levels have been successful. This article reviews the various studies that have led to the understanding of gene therapy outcomes in human ocular diseases and attempts to provide a brief sketch of successful clinical trials.

  2. Old genes experience stronger translational selection than young genes.

    Science.gov (United States)

    Yin, Hongyan; Ma, Lina; Wang, Guangyu; Li, Mengwei; Zhang, Zhang

    2016-09-15

    Selection on synonymous codon usage for translation efficiency and/or accuracy has been identified as a widespread mechanism in many living organisms. However, it remains unknown whether translational selection associates closely with gene age and acts differentially on genes with different evolutionary ages. To address this issue, here we investigate the strength of translational selection acting on different aged genes in human. Our results show that old genes present stronger translational selection than young genes, demonstrating that translational selection correlates positively with gene age. We further explore the difference of translational selection in duplicates vs. singletons and in housekeeping vs. tissue-specific genes. We find that translational selection acts comparably in old singletons and old duplicates and stronger translational selection in old genes is contributed primarily by housekeeping genes. For young genes, contrastingly, singletons experience stronger translational selection than duplicates, presumably due to redundant function of duplicated genes during their early evolutionary stage. Taken together, our results indicate that translational selection acting on a gene would not be constant during all stages of evolution, associating closely with gene age. Copyright © 2016 Elsevier B.V. All rights reserved.

  3. Genes2FANs: connecting genes through functional association networks

    Directory of Open Access Journals (Sweden)

    Dannenfelser Ruth

    2012-07-01

    Full Text Available Abstract Background Protein-protein, cell signaling, metabolic, and transcriptional interaction networks are useful for identifying connections between lists of experimentally identified genes/proteins. However, besides physical or co-expression interactions there are many ways in which pairs of genes, or their protein products, can be associated. By systematically incorporating knowledge on shared properties of genes from diverse sources to build functional association networks (FANs, researchers may be able to identify additional functional interactions between groups of genes that are not readily apparent. Results Genes2FANs is a web based tool and a database that utilizes 14 carefully constructed FANs and a large-scale protein-protein interaction (PPI network to build subnetworks that connect lists of human and mouse genes. The FANs are created from mammalian gene set libraries where mouse genes are converted to their human orthologs. The tool takes as input a list of human or mouse Entrez gene symbols to produce a subnetwork and a ranked list of intermediate genes that are used to connect the query input list. In addition, users can enter any PubMed search term and then the system automatically converts the returned results to gene lists using GeneRIF. This gene list is then used as input to generate a subnetwork from the user’s PubMed query. As a case study, we applied Genes2FANs to connect disease genes from 90 well-studied disorders. We find an inverse correlation between the counts of links connecting disease genes through PPI and links connecting diseases genes through FANs, separating diseases into two categories. Conclusions Genes2FANs is a useful tool for interpreting the relationships between gene/protein lists in the context of their various functions and networks. Combining functional association interactions with physical PPIs can be useful for revealing new biology and help form hypotheses for further experimentation. Our

  4. Industrial scale gene synthesis.

    Science.gov (United States)

    Notka, Frank; Liss, Michael; Wagner, Ralf

    2011-01-01

    The most recent developments in the area of deep DNA sequencing and downstream quantitative and functional analysis are rapidly adding a new dimension to understanding biochemical pathways and metabolic interdependencies. These increasing insights pave the way to designing new strategies that address public needs, including environmental applications and therapeutic inventions, or novel cell factories for sustainable and reconcilable energy or chemicals sources. Adding yet another level is building upon nonnaturally occurring networks and pathways. Recent developments in synthetic biology have created economic and reliable options for designing and synthesizing genes, operons, and eventually complete genomes. Meanwhile, high-throughput design and synthesis of extremely comprehensive DNA sequences have evolved into an enabling technology already indispensable in various life science sectors today. Here, we describe the industrial perspective of modern gene synthesis and its relationship with synthetic biology. Gene synthesis contributed significantly to the emergence of synthetic biology by not only providing the genetic material in high quality and quantity but also enabling its assembly, according to engineering design principles, in a standardized format. Synthetic biology on the other hand, added the need for assembling complex circuits and large complexes, thus fostering the development of appropriate methods and expanding the scope of applications. Synthetic biology has also stimulated interdisciplinary collaboration as well as integration of the broader public by addressing socioeconomic, philosophical, ethical, political, and legal opportunities and concerns. The demand-driven technological achievements of gene synthesis and the implemented processes are exemplified by an industrial setting of large-scale gene synthesis, describing production from order to delivery.

  5. Endovascular Gene Delivery from a Stent Platform: Gene- Eluting Stents.

    Science.gov (United States)

    Fishbein, Ilia; Chorny, Michael; Adamo, Richard F; Forbes, Scott P; Corrales, Ricardo A; Alferiev, Ivan S; Levy, Robert J

    A synergistic impact of research in the fields of post-angioplasty restenosis, drug-eluting stents and vascular gene therapy over the past 15 years has shaped the concept of gene-eluting stents. Gene-eluting stents hold promise of overcoming some biological and technical problems inherent to drug-eluting stent technology. As the field of gene-eluting stents matures it becomes evident that all three main design modules of a gene-eluting stent: a therapeutic transgene, a vector and a delivery system are equally important for accomplishing sustained inhibition of neointimal formation in arteries treated with gene delivery stents. This review summarizes prior work on stent-based gene delivery and discusses the main optimization strategies required to move the field of gene-eluting stents to clinical translation.

  6. Tumor-specific gene expression patterns with gene expression profiles

    Institute of Scientific and Technical Information of China (English)

    RUAN Xiaogang; LI Yingxin; LI Jiangeng; GONG Daoxiong; WANG Jinlian

    2006-01-01

    Gene expression profiles of 14 common tumors and their counterpart normal tissues were analyzed with machine learning methods to address the problem of selection of tumor-specific genes and analysis of their differential expressions in tumor tissues. First, a variation of the Relief algorithm, "RFE_Relief algorithm" was proposed to learn the relations between genes and tissue types. Then, a support vector machine was employed to find the gene subset with the best classification performance for distinguishing cancerous tissues and their counterparts. After tissue-specific genes were removed, cross validation experiments were employed to demonstrate the common deregulated expressions of the selected gene in tumor tissues. The results indicate the existence of a specific expression fingerprint of these genes that is shared in different tumor tissues, and the hallmarks of the expression patterns of these genes in cancerous tissues are summarized at the end of this paper.

  7. Entrez Gene: gene-centered information at NCBI.

    Science.gov (United States)

    Maglott, Donna; Ostell, Jim; Pruitt, Kim D; Tatusova, Tatiana

    2011-01-01

    Entrez Gene (http://www.ncbi.nlm.nih.gov/gene) is National Center for Biotechnology Information (NCBI)'s database for gene-specific information. Entrez Gene maintains records from genomes which have been completely sequenced, which have an active research community to submit gene-specific information, or which are scheduled for intense sequence analysis. The content represents the integration of curation and automated processing from NCBI's Reference Sequence project (RefSeq), collaborating model organism databases, consortia such as Gene Ontology and other databases within NCBI. Records in Entrez Gene are assigned unique, stable and tracked integers as identifiers. The content (nomenclature, genomic location, gene products and their attributes, markers, phenotypes and links to citations, sequences, variation details, maps, expression, homologs, protein domains and external databases) is available via interactive browsing through NCBI's Entrez system, via NCBI's Entrez programming utilities (E-Utilities) and for bulk transfer by FTP.

  8. Expression of Cyto-metabolism Related Genes in Placenta of Preeclampsia Women%子痫前期胎盘中代谢相关基因的异常表达

    Institute of Scientific and Technical Information of China (English)

    毛东伟; 张玮; 段志宇; 杨东霞; 朱宏

    2009-01-01

    Objective:To study the expression of cyto-metabolism related genes in preeclamptic placenta and the possible mechanism involved in the regulation process. Methods: 12000 clones from the IMAGE library were used to build the cDNA microarray, which are involved in the functions of signal transduction, cell cycle, transcription, neuro-protection, apoptosis, angiogenesis, metabolism, extracellular matrix, and others. Complementary DNA (cDNA) probes were generated from human placentas biopsies of normal and preeclamptic pregnancies. After co-hybridized with the cDNA microarray, slides were scanned and the results were analyzed by software. To validate the cDNA microarray results, we also performed Northem-blot analysis on a small subset of affected genes. Results:44 genes' expressions were significantly difference between normal and preeclamptic placentas. Among of them, Glycogen phosphorylase gene, leptin gene, Lipoprotein lipase gene, and Glucose transporter gene were up-regulated, while CD73 gene and Creatine kinase B gene were down-regulated. Conclusions:The change of cyto-metabolism related genes expression in placenta might be involved in the pathogenesis of preeclampsia.%目的:探讨细胞代谢相关基因在子痫前期胎盘组织中的表达谱及其影响机制.方法:使用含12000个与代谢、凋亡、细胞黏附、信号传导、转录因子等有关基因的cDNA表达谱芯片,检测4例妊娠期高血压疾病子痫前期及正常的胎盘组织的基因表达谱差异.并对部分差异表达基因进行了Northern验证.结果:4例子痫前期胎盘中共有44条基因表达发生了变化,其中糖原磷酸化酶(GP-M)基因、瘦素(leptin)基因、脂蛋白酯酶(LPL)基因及糖代谢相关基因(glucose transporter)表达增强,核苷酸代谢基因(CD73)与能量代谢调节基因(creatine kinase B)表达下降.结论:多种基因表达异常与子痫前期的病理发生有关,细胞代谢相关基因表达异常可能是血管内皮细胞损伤的原因之一.

  9. 代谢相关基因在先兆子痫胎盘中的表达情况分析%Expression of cyto-metabolism related genes in pre-eclamptic placenta

    Institute of Scientific and Technical Information of China (English)

    车建华; 毛东伟; 谭文华; 韩世愈

    2009-01-01

    目的 探讨细胞代谢相关基因在先兆子痫胎盘组织中的表达变化及其影响机制.方法 使用含12000个与代谢、凋亡、细胞粘附、信号传导、转录因子等有关基因的cDNA表达谱芯片,检测4例重度妊娠高血压疾病子痫前期及正常的胎盘组织的基因表达谱差异,并差异表达的细胞代谢相关基因进行了Northern验证.结果 4先兆子痫胎盘中同时有44种基因表达发生了变化,其中糖原磷酸化酶(GP-M)基因、瘦素(leptin)基因、脂蛋白酯酶(LPL)基因及糖代谢相关基因(Glucose transporter)表达增强,核苷酸代谢基因(CD73)与能量代谢调节基因(Creatine kinase B)表达下降.结论 多种基因表达异常与先兆子痫的病理发生有关,细胞代谢相关基因表达异常可能是血管内皮损伤的原因之一.%Objective: To study the expression of cyto-metabolism related genes in pre-eclamptic placenta and the possible mechanism involved in the regulation process. Methods: 12000 elones from the IMAGE library were used to build the cDNA microarray, which are involved in the functions of signal transduction, cell cycle, transcription, neuroproteetion, apoptosis, angiogenesis, metabolism, extracellular matrix and others. Complementary DNA (cDNA) probes were generated from human placentas biopsies of normal and preeclamptic pregnancies, After co-hybridized with the cDNA microarray, slides were scanned and the results were analyzed by software. To validate the cDNA microarray results, we also performed Northern-blot analysis on the affected cyto-metabolism related genes. Results: 44 genes's erexpression are significantly difference between normal and pre-eclimptic placentas. Among of them, Glycogen phosphorylase gene, leptin gene, Lipoprotein lipase gene and Glucose transporter gene are upregulated , while CD73 gene and Creatine kinase B gene were downregulated. Conclusions: The change of cyto-metabolism related genes expression in placenta might be

  10. Streptozotocin-Treated High Fat Fed Mice: A New Type 2 Diabetes Model Used to Study Canagliflozin-Induced Alterations in Lipids and Lipoproteins.

    Science.gov (United States)

    Yu, Tian; Sungelo, Mitchell J; Goldberg, Ira J; Wang, Hong; Eckel, Robert H

    2017-05-01

    The pharmacological effects of type 2 diabetes (T2DM) medications on lipoprotein metabolism are difficult to assess in preclinical models because those created failure to replicate the human condition in which insulin deficiency is superimposed on obesity-related insulin resistance. To create a better model, we fed mice with high fat (HF) diet and treated the animals with low dose streptozotocin (STZ) to mimic T2DM. We used this model to evaluate the effects of canagliflozin (CANA), a drug that reduces plasma glucose by inhibiting the sodium-glucose transporter 2 (SGLT2), which mediates ~90% of renal glucose reabsorption] on lipid and lipoprotein metabolism. After 6 weeks of CANA (30 mg/kg/day) treatment, the increase in total plasma cholesterol in HF-STZ diabetic mice was reversed, but plasma triglycerides were not affected. Lipoprotein fractionation and cholesterol distribution analysis showed that CANA kept HDL-Cholesterol, LDL-Cholesterol, and IDL-Cholesterol levels steady while these lipoprotein species were increased in placebo- and insulin-treated control groups. CANA treatment of HF-STZ mice reduced post-heparin plasma lipoprotein lipase (LPL) activity at 2 (-40%) and 5 (-30%) weeks compared to placebo. Tissue-specific LPL activity following CANA treatment showed similar reduction. In summary, CANA prevented the total cholesterol increase in HF-STZ mice without effects on plasma lipids or lipoproteins, but did decrease LPL, implying a potential role of LPL-dependent lipoprotein metabolism in CANA action. These effects did not recapitulate the effect of SGLT2 inhibitors on lipids and lipoproteins in human, suggesting that a better murine T2DM model (such as the ApoB100 humanized CETP-overexpressing mouse) is needed next. © Georg Thieme Verlag KG Stuttgart · New York.

  11. Gene set analysis for longitudinal gene expression data

    Directory of Open Access Journals (Sweden)

    Piepho Hans-Peter

    2011-07-01

    Full Text Available Abstract Background Gene set analysis (GSA has become a successful tool to interpret gene expression profiles in terms of biological functions, molecular pathways, or genomic locations. GSA performs statistical tests for independent microarray samples at the level of gene sets rather than individual genes. Nowadays, an increasing number of microarray studies are conducted to explore the dynamic changes of gene expression in a variety of species and biological scenarios. In these longitudinal studies, gene expression is repeatedly measured over time such that a GSA needs to take into account the within-gene correlations in addition to possible between-gene correlations. Results We provide a robust nonparametric approach to compare the expressions of longitudinally measured sets of genes under multiple treatments or experimental conditions. The limiting distributions of our statistics are derived when the number of genes goes to infinity while the number of replications can be small. When the number of genes in a gene set is small, we recommend permutation tests based on our nonparametric test statistics to achieve reliable type I error and better power while incorporating unknown correlations between and within-genes. Simulation results demonstrate that the proposed method has a greater power than other methods for various data distributions and heteroscedastic correlation structures. This method was used for an IL-2 stimulation study and significantly altered gene sets were identified. Conclusions The simulation study and the real data application showed that the proposed gene set analysis provides a promising tool for longitudinal microarray analysis. R scripts for simulating longitudinal data and calculating the nonparametric statistics are posted on the North Dakota INBRE website http://ndinbre.org/programs/bioinformatics.php. Raw microarray data is available in Gene Expression Omnibus (National Center for Biotechnology Information with

  12. Optimal Reference Genes for Gene Expression Normalization in Trichomonas vaginalis.

    Science.gov (United States)

    dos Santos, Odelta; de Vargas Rigo, Graziela; Frasson, Amanda Piccoli; Macedo, Alexandre José; Tasca, Tiana

    2015-01-01

    Trichomonas vaginalis is the etiologic agent of trichomonosis, the most common non-viral sexually transmitted disease worldwide. This infection is associated with several health consequences, including cervical and prostate cancers and HIV acquisition. Gene expression analysis has been facilitated because of available genome sequences and large-scale transcriptomes in T. vaginalis, particularly using quantitative real-time polymerase chain reaction (qRT-PCR), one of the most used methods for molecular studies. Reference genes for normalization are crucial to ensure the accuracy of this method. However, to the best of our knowledge, a systematic validation of reference genes has not been performed for T. vaginalis. In this study, the transcripts of nine candidate reference genes were quantified using qRT-PCR under different cultivation conditions, and the stability of these genes was compared using the geNorm and NormFinder algorithms. The most stable reference genes were α-tubulin, actin and DNATopII, and, conversely, the widely used T. vaginalis reference genes GAPDH and β-tubulin were less stable. The PFOR gene was used to validate the reliability of the use of these candidate reference genes. As expected, the PFOR gene was upregulated when the trophozoites were cultivated with ferrous ammonium sulfate when the DNATopII, α-tubulin and actin genes were used as normalizing gene. By contrast, the PFOR gene was downregulated when the GAPDH gene was used as an internal control, leading to misinterpretation of the data. These results provide an important starting point for reference gene selection and gene expression analysis with qRT-PCR studies of T. vaginalis.

  13. Recent advances in physiological lipoprotein metabolism.

    Science.gov (United States)

    Ramasamy, Indra

    2014-12-01

    Research into lipoprotein metabolism has developed because understanding lipoprotein metabolism has important clinical indications. Lipoproteins are risk factors for cardiovascular disease. Recent advances include the identification of factors in the synthesis and secretion of triglyceride rich lipoproteins, chylomicrons (CM) and very low density lipoproteins (VLDL). These included the identification of microsomal transfer protein, the cotranslational targeting of apoproteinB (apoB) for degradation regulated by the availability of lipids, and the characterization of transport vesicles transporting primordial apoB containing particles to the Golgi. The lipase maturation factor 1, glycosylphosphatidylinositol-anchored high density lipoprotein binding protein 1 and an angiopoietin-like protein play a role in lipoprotein lipase (LPL)-mediated hydrolysis of secreted CMs and VLDL so that the right amount of fatty acid is delivered to the right tissue at the right time. Expression of the low density lipoprotein (LDL) receptor is regulated at both transcriptional and post-transcriptional level. Proprotein convertase subtilisin/kexin type 9 (PCSK9) has a pivotal role in the degradation of LDL receptor. Plasma remnant lipoproteins bind to specific receptors in the liver, the LDL receptor, VLDL receptor and LDL receptor-like proteins prior to removal from the plasma. Reverse cholesterol transport occurs when lipid free apoAI recruits cholesterol and phospholipid to assemble high density lipoprotein (HDL) particles. The discovery of ABC transporters (ABCA1 and ABCG1) and scavenger receptor class B type I (SR-BI) provided further information on the biogenesis of HDL. In humans HDL-cholesterol can be returned to the liver either by direct uptake by SR-BI or through cholesteryl ester transfer protein exchange of cholesteryl ester for triglycerides in apoB lipoproteins, followed by hepatic uptake of apoB containing particles. Cholesterol content in cells is regulated by several

  14. Dominance from the perspective of gene-gene and gene-chemical interactions.

    Science.gov (United States)

    Gladki, Arkadiusz; Zielenkiewicz, Piotr; Kaczanowski, Szymon

    2016-02-01

    In this study, we used genetic interaction (GI) and gene-chemical interaction (GCI) data to compare mutations with different dominance phenotypes. Our analysis focused primarily on Saccharomyces cerevisiae, where haploinsufficient genes (HI; genes with dominant loss-of-function mutations) were found to be participating in gene expression processes, namely, the translation and regulation of gene transcription. Non-ribosomal HI genes (mainly regulators of gene transcription) were found to have more GIs and GCIs than haplosufficient (HS) genes. Several properties seem to lead to the enrichment of interactions, most notably, the following: importance, pleiotropy, gene expression level and gene expression variation. Importantly, after these properties were appropriately considered in the analysis, the correlation between dominance and GI/GCI degrees was still observed. Strikingly, for the GCIs of heterozygous strains, haploinsufficiency was the only property significantly correlated with the number of GCIs. We found ribosomal HI genes to be depleted in GIs/GCIs. This finding can be explained by their high variation in gene expression under different genetic backgrounds and environmental conditions. We observed the same distributions of GIs among non-ribosomal HI, ribosomal HI and HS genes in three other species: Schizosaccharomyces pombe, Drosophila melanogaster and Homo sapiens. One potentially interesting exception was the lack of significant differences in the degree of GIs between non-ribosomal HI and HS genes in Schizosaccharomyces pombe.

  15. Gene-gene interaction between tuberculosis candidate genes in a South African population.

    Science.gov (United States)

    de Wit, Erika; van der Merwe, Lize; van Helden, Paul D; Hoal, Eileen G

    2011-02-01

    In a complex disease such as tuberculosis (TB) it is increasingly evident that gene-gene interactions play a far more important role in an individual's susceptibility to develop the disease than single polymorphisms on their own, as one gene can enhance or hinder the expression of another gene. Gene-gene interaction analysis is a new approach to elucidate susceptibility to TB. The possibility of gene-gene interactions was assessed, focusing on 11 polymorphisms in nine genes (DC-SIGN, IFN-γ, IFNGR1, IL-8, IL-1Ra, MBL, NRAMP1, RANTES, and SP-D) that have been associated with TB, some repeatedly. An optimal model, which best describes and predicts TB case-control status, was constructed. Significant interactions were detected between eight pairs of variants. The models fitted the observed data extremely well, with p activation is greatly enhanced by IFN-γ and IFN-γ response elements that are present in the human NRAMP1 promoter region, providing further evidence for their interaction. This study enabled us to test the theory that disease outcome may be due to interaction of several gene effects. With eight instances of statistically significant gene-gene interactions, the importance of epistasis is clearly identifiable in this study. Methods for studying gene-gene interactions are based on a multilocus and multigene approach, consistent with the nature of complex-trait diseases, and may provide the paradigm for future genetic studies of TB.

  16. Gene doping in modern sport.

    Directory of Open Access Journals (Sweden)

    MAREK SAWCZUK

    2009-01-01

    Full Text Available Background: The subject of this paper is gene doping, which should be understood as "he non-therapeutic use of cells, genes, genetic elements, or of the modulation of gene expression, having the capacity to improve athletic performance". The authors of this work, based on the review of literature and previous research, make an attempt at wider characterization of gene doping and the discussion of related potential threats.Methods: This is a comprehensive survey of literature on the latest applications of molecular biology in medicine. The analysis involves a dozen scientific databases examined in order to find genes used in gene therapy and potentially useful in gene doping. Results: The obtained results enable better recognition of gene doping and indicate genes used in medicine that could be used in gene doping. This paper describes potential effects of their use and associated risk, and predicts the possible developments of gene doping in the future. Conclusion: Gene doping is undoubtedly a part of modern sport. Although WADA included gene doping on the list of banned methods as early as 2004, as previously stated above, it has not managed to develop efficient methods of detection.

  17. [Gene pool and gene geography of the USSR population].

    Science.gov (United States)

    Rychkov, Iu G; Balanovskaia, E V

    1992-01-01

    Gene pool and gene geography are discussed from the point of view of their conceptual history beginning from the original concept of A.S. Serebrovskiĭ (1928). Difference between the present-day gene geography and gene geography of gene pool is accentuated: the former only represents a portion of the latter. Historical and territorial integrity of the USSR population gene pool, in conjunction with its huge diversity, is the main problem being analysed by various means of computerized genetic cartography. Coupled with the gene frequency mapping, following methods were also used: mapping of average heterozygosity, of interpopulation differentiation, of principal component scores and mapping of geographical trend for each mapped genetic parameter. The work is based on 100 allelic genes and haplotypes from 30 independent loci studied on the average in 225 local populations. Statistical analysis of gene geographical maps is based on 3975 nodes of regular cartographic net for the USSR territory. The wind rose of systematic changes in the USSR gene pool has three main geographic orientations: W-E, SW-NE and S-N. At the same time, there are only two main systematic forces of gene pool evolution: the force of social history with predominant W-E orientation and the force of natural history with predominant S-N orientation of their actions. The heterozygosity level of gene pool declines strictly in accordance with the resultant in the SW-NE direction.

  18. Immunotherapy and gene therapy.

    Science.gov (United States)

    Simpson, Elizabeth

    2004-02-01

    The Immunotherapy and Gene Therapy meeting of the Academy of Medical Sciences reviewed the state-of-the-art and translational prospects for therapeutic interventions aimed at killing tumor cells, correcting genetic defects and developing vaccines for chronic infections. Crucial basic science concepts and information about dendritic cells, the structure and function of T-cell receptors, and manipulation of the immune response by cytokine antagonists and peptides were presented. This information underpins vaccine design and delivery, as well as attempts to immunomodulate autoimmune disease. Results from studies using anticancer DNA vaccines, which include appropriate signals for both the innate and adaptive immune response, were presented in several talks. The vaccines incorporated helper epitopes and cancer target epitopes such as immunoglobulin idiotypes (for lymphomas and myelomas), melanoma-associated antigens (for melanoma and other solid tumors) and minor histocompatibility antigens (for leukemia). The results of using vaccines employing similar principles and designed to reduce viral load in HIV/AIDS patients were also presented. The introduction of suicide genes incorporating the bacterial enzyme nitroreductase gene (ntr) targeted at tumor cells prior to administration of the prodrug CB-1954, converted by ntr into a toxic alkylating agent, was discussed against the background of clinical trials and improved suicide gene design. The introduction into hematopoietic stem cells of missing genes for the common gamma-chain, deficiency of which causes severe combined immunodeficiency (SCID), used similar retroviral transduction. The outcome of treating six SCID patients in the UK, and ten in France was successful immune reconstitution in the majority of patients, but in two of the French cases a complication of lymphoproliferative disease due to insertional mutagenesis was observed. The adoptive transfer of T-cells specific for minor histocompatibility antigens (for

  19. SOX genes: architects of development.

    Science.gov (United States)

    Prior, H M; Walter, M A

    1996-07-01

    Development in higher organisms involves complex genetic regulation at the molecular level. The emerging picture of development control includes several families of master regulatory genes which can affect the expression of down-stream target genes in developmental cascade pathways. One new family of such development regulators is the SOX gene family. The SOX genes are named for a shared motif called the SRY box a region homologous to the DNA-binding domain of SRY, the mammalian sex determining gene. Like SRY, SOX genes play important roles in chordate development. At least a dozen human SOX genes have been identified and partially characterized (Tables 1 and 2). Mutations in SOX9 have recently been linked to campomelic dysplasia and autosomal sex reversal, and other SOX genes may also be associated with human disease.

  20. Brains, genes, and primates.

    Science.gov (United States)

    Izpisua Belmonte, Juan Carlos; Callaway, Edward M; Caddick, Sarah J; Churchland, Patricia; Feng, Guoping; Homanics, Gregg E; Lee, Kuo-Fen; Leopold, David A; Miller, Cory T; Mitchell, Jude F; Mitalipov, Shoukhrat; Moutri, Alysson R; Movshon, J Anthony; Okano, Hideyuki; Reynolds, John H; Ringach, Dario; Sejnowski, Terrence J; Silva, Afonso C; Strick, Peter L; Wu, Jun; Zhang, Feng

    2015-05-06

    One of the great strengths of the mouse model is the wide array of genetic tools that have been developed. Striking examples include methods for directed modification of the genome, and for regulated expression or inactivation of genes. Within neuroscience, it is now routine to express reporter genes, neuronal activity indicators, and opsins in specific neuronal types in the mouse. However, there are considerable anatomical, physiological, cognitive, and behavioral differences between the mouse and the human that, in some areas of inquiry, limit the degree to which insights derived from the mouse can be applied to understanding human neurobiology. Several recent advances have now brought into reach the goal of applying these tools to understanding the primate brain. Here we describe these advances, consider their potential to advance our understanding of the human brain and brain disorders, discuss bioethical considerations, and describe what will be needed to move forward.

  1. Alphaviruses in Gene Therapy

    Directory of Open Access Journals (Sweden)

    Kenneth Lundstrom

    2009-04-01

    Full Text Available Alphaviruses are enveloped single stranded RNA viruses, which as gene therapy vectors provide high-level transient gene expression. Semliki Forest virus (SFV, Sindbis virus (SIN and Venezuelan Equine Encephalitis (VEE virus have been engineered as efficient replication-deficient and -competent expression vectors. Alphavirus vectors have frequently been used as vehicles for tumor vaccine generation. Moreover, SFV and SIN vectors have been applied for intratumoral injections in animals implanted with tumor xenografts. SIN vectors have demonstrated natural tumor targeting, which might permit systemic vector administration. Another approach for systemic delivery of SFV has been to encapsulate replication-deficient viral particles in liposomes, which can provide passive targeting to tumors and allow repeated administration without host immune responses. This approach has demonstrated safe delivery of encapsulated SFV particles to melanoma and kidney carcinoma patients in a phase I trial. Finally, the prominent neurotropism of alphaviruses make them attractive for the treatment of CNS-related diseases.

  2. Gene Disease Diagnostic System

    Institute of Scientific and Technical Information of China (English)

    黄国亮; 张腾飞; 程京; 周玉祥; 刘诚迅; 金国藩; 邬敏贤; 严瑛白; 杨蓉

    2002-01-01

    Binary optics, where the optical element can be fabricated on a thin glass plate with micro-ion-etching film layer, has been widely applied in recent years. A novel optical scanning system for gene disease diagnostics described in this paper has four kinds of optical devices, including beam splitters, an array lens, an array filter and detection arrays. A software was developed to design the binary optics system using an iterative method. Two beam splitters were designed and fabricated, which can divide a beam into a 9×9 array or into a 13×13 array. The beam splitters have good diffraction efficiencies (>70%) and an even energy distribution. The gene disease diagnostic system is a portable biochip and binary optics technology. The binary optical devices in the non-confocal scanning system can raise the fluorescence detection sensitivity of the micro-array hybrid biochip.

  3. Gene therapy for mucopolysaccharidosis

    Science.gov (United States)

    Ponder, Katherine P; Haskins, Mark E

    2012-01-01

    Mucopolysaccharidoses (MPS) are due to deficiencies in activities of lysosomal enzymes that degrade glycosaminoglycans. Some attempts at gene therapy for MPS in animal models have involved intravenous injection of vectors derived from an adeno-associated virus (AAV), adenovirus, retrovirus or a plasmid, which primarily results in expression in liver and secretion of the relevant enzyme into blood. Most vectors can correct disease in liver and spleen, although correction in other organs including the brain requires high enzyme activity in the blood. Alternative approaches are to transduce hematopoietic stem cells, or to inject a vector locally into difficult-to-reach sites such as the brain. Gene therapy holds great promise for providing a long-lasting therapeutic effect for MPS if safety issues can be resolved. PMID:17727324

  4. Gene Porter Bridwell

    Science.gov (United States)

    1994-01-01

    Gene Porter Bridwell served as the director of the Marshall Space Flight Center from January 6, 1994 until February 3, 1996, when he retired from NASA after thirty-four years service. Bridwell, a Marshall employee since 1962, had been Marshall's Space Shuttle Projects Office Director and Space Station Redesign Team deputy manager. Under Bridwell, Marshall worked to develop its role as a Center of Excellence for propulsion and for providing access to space.

  5. Gene Porter Bridwell

    Science.gov (United States)

    1994-01-01

    Gene Porter Bridwell served as the director of the Marshall Space Flight Center from January 6, 1994 until February 3, 1996, when he retired from NASA after thirty-four years service. Bridwell, a Marshall employee since 1962, had been Marshall's Space Shuttle Projects Office Director and Space Station Redesign Team deputy manager. Under Bridwell, Marshall worked to develop its role as a Center of Excellence for propulsion and for providing access to space.

  6. Epigenetics: beyond genes

    CSIR Research Space (South Africa)

    Fossey, A

    2009-06-01

    Full Text Available to neighbouring euchromatic genes, known as position effect variegation and can be transmitted through mitosis, forming the basis of epigenetic inheritance from one cell generation to another; creating cellular memory (Brzeski and Jerzmanowski, 2004... life form, supports meiosis that produces haploid male and female spores and initiates the gametophytic generation. Gametogenesis and subsequent fertilisation take place when gametophytic and sporophytic structures interact. The product...

  7. PRRT2 gene mutations

    Science.gov (United States)

    Gardiner, Alice R.; Bhatia, Kailash P.; Stamelou, Maria; Dale, Russell C.; Kurian, Manju A.; Schneider, Susanne A.; Wali, G.M.; Counihan, Tim; Schapira, Anthony H.; Spacey, Sian D.; Valente, Enza-Maria; Silveira-Moriyama, Laura; Teive, Hélio A.G.; Raskin, Salmo; Sander, Josemir W.; Lees, Andrew; Warner, Tom; Kullmann, Dimitri M.; Wood, Nicholas W.; Hanna, Michael

    2012-01-01

    ABSTRACT Objective: The proline-rich transmembrane protein (PRRT2) gene was recently identified using exome sequencing as the cause of autosomal dominant paroxysmal kinesigenic dyskinesia (PKD) with or without infantile convulsions (IC) (PKD/IC syndrome). Episodic neurologic disorders, such as epilepsy, migraine, and paroxysmal movement disorders, often coexist and are thought to have a shared channel-related etiology. To investigate further the frequency, spectrum, and phenotype of PRRT2 mutations, we analyzed this gene in 3 large series of episodic neurologic disorders with PKD/IC, episodic ataxia (EA), and hemiplegic migraine (HM). Methods: The PRRT2 gene was sequenced in 58 family probands/sporadic individuals with PKD/IC, 182 with EA, 128 with HM, and 475 UK and 96 Asian controls. Results: PRRT2 genetic mutations were identified in 28 out of 58 individuals with PKD/IC (48%), 1/182 individuals with EA, and 1/128 individuals with HM. A number of loss-of-function and coding missense mutations were identified; the most common mutation found was the p.R217Pfs*8 insertion. Males were more frequently affected than females (ratio 52:32). There was a high proportion of PRRT2 mutations found in families and sporadic cases with PKD associated with migraine or HM (10 out of 28). One family had EA with HM and another large family had typical HM alone. Conclusions: This work expands the phenotype of mutations in the PRRT2 gene to include the frequent occurrence of migraine and HM with PKD/IC, and the association of mutations with EA and HM and with familial HM alone. We have also extended the PRRT2 mutation type and frequency in PKD and other episodic neurologic disorders. PMID:23077024

  8. Gene therapy in gastric cancer

    Institute of Scientific and Technical Information of China (English)

    Xu Chang-tai; Guo Xue-gang; Pan Bo-rong

    2003-01-01

    @@ 1 Introduction We have reviewed the gene therapy in gastrointestinal diseases[1]. Gastric cancer is common in China[2~20] ,and its early diagnosis andtreatment are still difficult up to now[13~36]. The expression of anexogenous gene introduced by gene therapy into patients with gliomascan be monitored non- invasively by positron- emission tomography[4]. In recent years, gene study in cancer is a hotspot, and great progress hasbeen achieved[33~41].

  9. Gene therapy for gastric diseases.

    OpenAIRE

    Fumoto, Shintaro; Nishi, Junya; Nakamura, Junzo; Nishida, Koyo

    2008-01-01

    Gene therapy for gastric cancer and gastric ulcer is a rationalized strategy since various genes correlate with these diseases. Since gene expressions in non-target tissues/cells cause side effects, a selective gene delivery system targeted to the stomach and/or cancer must be developed. The route of vector transfer (direct injection, systemic, intraperitoneal, gastric serosal surface and oral administration) is an important issue which can determine efficacy and safety. Strategies for cancer...

  10. Genealogy and gene trees.

    Science.gov (United States)

    Rasmuson, Marianne

    2008-02-01

    Heredity can be followed in persons or in genes. Persons can be identified only a few generations back, but simplified models indicate that universal ancestors to all now living persons have occurred in the past. Genetic variability can be characterized as variants of DNA sequences. Data are available only from living persons, but from the pattern of variation gene trees can be inferred by means of coalescence models. The merging of lines backwards in time leads to a MRCA (most recent common ancestor). The time and place of living for this inferred person can give insights in human evolutionary history. Demographic processes are incorporated in the model, but since culture and customs are known to influence demography the models used ought to be tested against available genealogy. The Icelandic data base offers a possibility to do so and points to some discrepancies. Mitochondrial DNA and Y chromosome patterns give a rather consistent view of human evolutionary history during the latest 100 000 years but the earlier epochs of human evolution demand gene trees with longer branches. The results of such studies reveal as yet unsolved problems about the sources of our genome.

  11. Gene-gene and gene-environmental interactions of childhood asthma: a multifactor dimension reduction approach.

    Directory of Open Access Journals (Sweden)

    Ming-Wei Su

    Full Text Available BACKGROUND: The importance of gene-gene and gene-environment interactions on asthma is well documented in literature, but a systematic analysis on the interaction between various genetic and environmental factors is still lacking. METHODOLOGY/PRINCIPAL FINDINGS: We conducted a population-based, case-control study comprised of seventh-grade children from 14 Taiwanese communities. A total of 235 asthmatic cases and 1,310 non-asthmatic controls were selected for DNA collection and genotyping. We examined the gene-gene and gene-environment interactions between 17 single-nucleotide polymorphisms in antioxidative, inflammatory and obesity-related genes, and childhood asthma. Environmental exposures and disease status were obtained from parental questionnaires. The model-free and non-parametrical multifactor dimensionality reduction (MDR method was used for the analysis. A three-way gene-gene interaction was elucidated between the gene coding glutathione S-transferase P (GSTP1, the gene coding interleukin-4 receptor alpha chain (IL4Ra and the gene coding insulin induced gene 2 (INSIG2 on the risk of lifetime asthma. The testing-balanced accuracy on asthma was 57.83% with a cross-validation consistency of 10 out of 10. The interaction of preterm birth and indoor dampness had the highest training-balanced accuracy at 59.09%. Indoor dampness also interacted with many genes, including IL13, beta-2 adrenergic receptor (ADRB2, signal transducer and activator of transcription 6 (STAT6. We also used likelihood ratio tests for interaction and chi-square tests to validate our results and all tests showed statistical significance. CONCLUSIONS/SIGNIFICANCE: The results of this study suggest that GSTP1, INSIG2 and IL4Ra may influence the lifetime asthma susceptibility through gene-gene interactions in schoolchildren. Home dampness combined with each one of the genes STAT6, IL13 and ADRB2 could raise the asthma risk.

  12. Gene therapy of cancer and development of therapeutic target gene

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Chang Min; Kwon, Hee Chung

    1998-04-01

    We applied HSV-tk/GCV strategy to orthotopic rat hepatoma model and showed anticancer effects of hepatoma. The increased expression of Lac Z gene after adenovirus-mediated gene delivery throughout hepatic artery was thought that is increased the possibility of gene therapy for curing hepatoma. With the construction of kGLP-laboratory, it is possible to produce a good quantity and quality of adenovirus in lage-scale production and purification of adenovirus vector. Also, the analysis of hepatoma related genes by PCR-LOH could be used for the diagnosis of patients and the development of therapeutic gene.

  13. Independent Gene Discovery and Testing

    Science.gov (United States)

    Palsule, Vrushalee; Coric, Dijana; Delancy, Russell; Dunham, Heather; Melancon, Caleb; Thompson, Dennis; Toms, Jamie; White, Ashley; Shultz, Jeffry

    2010-01-01

    A clear understanding of basic gene structure is critical when teaching molecular genetics, the central dogma and the biological sciences. We sought to create a gene-based teaching project to improve students' understanding of gene structure and to integrate this into a research project that can be implemented by instructors at the secondary level…

  14. Compositional gradients in Gramineae genes

    DEFF Research Database (Denmark)

    Wong, Gane Ka-Shu; Wang, Jun; Tao, Lin

    2002-01-01

    In this study, we describe a property of Gramineae genes, and perhaps all monocot genes, that is not observed in eudicot genes. Along the direction of transcription, beginning at the junction of the 5'-UTR and the coding region, there are gradients in GC content, codon usage, and amino-acid usage...

  15. Decationized polyplexes for gene delivery

    NARCIS (Netherlands)

    Novo, L.; Mastrobattista, E.; Nostrum, van C.F.; Lammers, T.G.G.M.; Hennink, W.E.

    2015-01-01

    Gene therapy has received much attention in the field of drug delivery. Synthetic, nonviral gene delivery systems have gained increasing attention as vectors for gene therapy mainly due to a favorable immunogenicity profile and ease of manufacturing as compared to viral vectors. The great majority o

  16. Ascidian gene-expression profiles

    OpenAIRE

    Jeffery, William R.

    2002-01-01

    With the advent of gene-expression profiling, a large number of genes can now be investigated simultaneously during critical stages of development. This approach will be particularly informative in studies of ascidians, basal chordates whose genomes and embryology are uniquely suited for mapping developmental gene networks.

  17. Gene electrotransfer in clinical trials

    DEFF Research Database (Denmark)

    Gehl, Julie

    2014-01-01

    Electroporation is increasingly being used for delivery of chemotherapy to tumors. Likewise, gene delivery by electroporation is rapidly gaining momentum for both vaccination purposes and for delivery of genes coding for other therapeutic molecules, such as chronic diseases or cancer. This chapte...... describes how gene therapy may be performed using electric pulses to enhance uptake and expression.......Electroporation is increasingly being used for delivery of chemotherapy to tumors. Likewise, gene delivery by electroporation is rapidly gaining momentum for both vaccination purposes and for delivery of genes coding for other therapeutic molecules, such as chronic diseases or cancer. This chapter...

  18. Gene therapy of liver cancer

    Institute of Scientific and Technical Information of China (English)

    Ruben Hernandez-Alcoceba; Bruno Sangro; Jesus Prieto

    2006-01-01

    The application of gene transfer technologies to the treatment of cancer has led to the development of new experimental approaches like gene directed enzyme/prodrug therapy (GDEPT), inhibition of oncogenes and restoration of tumor-suppressor genes. In addition,gene therapy has a big impact on other fields like cancer immunotherapy, anti-angiogenic therapy and virotherapy.These strategies are being evaluated for the treatment of primary and metastatic liver cancer and some of them have reached clinical phases. We present a review on the basis and the actual status of gene therapy approaches applied to liver cancer.

  19. Classifying genes to the correct Gene Ontology Slim term in Saccharomyces cerevisiae using neighbouring genes with classification learning

    OpenAIRE

    Tsatsoulis Costas; Amthauer Heather A

    2010-01-01

    Abstract Background There is increasing evidence that gene location and surrounding genes influence the functionality of genes in the eukaryotic genome. Knowing the Gene Ontology Slim terms associated with a gene gives us insight into a gene's functionality by informing us how its gene product behaves in a cellular context using three different ontologies: molecular function, biological process, and cellular component. In this study, we analyzed if we could classify a gene in Saccharomyces ce...

  20. Gene finding in novel genomes

    Directory of Open Access Journals (Sweden)

    Korf Ian

    2004-05-01

    Full Text Available Abstract Background Computational gene prediction continues to be an important problem, especially for genomes with little experimental data. Results I introduce the SNAP gene finder which has been designed to be easily adaptable to a variety of genomes. In novel genomes without an appropriate gene finder, I demonstrate that employing a foreign gene finder can produce highly inaccurate results, and that the most compatible parameters may not come from the nearest phylogenetic neighbor. I find that foreign gene finders are more usefully employed to bootstrap parameter estimation and that the resulting parameters can be highly accurate. Conclusion Since gene prediction is sensitive to species-specific parameters, every genome needs a dedicated gene finder.

  1. GeneDistiller--distilling candidate genes from linkage intervals.

    Directory of Open Access Journals (Sweden)

    Dominik Seelow

    Full Text Available BACKGROUND: Linkage studies often yield intervals containing several hundred positional candidate genes. Different manual or automatic approaches exist for the determination of the gene most likely to cause the disease. While the manual search is very flexible and takes advantage of the researchers' background knowledge and intuition, it may be very cumbersome to collect and study the relevant data. Automatic solutions on the other hand usually focus on certain models, remain "black boxes" and do not offer the same degree of flexibility. METHODOLOGY: We have developed a web-based application that combines the advantages of both approaches. Information from various data sources such as gene-phenotype associations, gene expression patterns and protein-protein interactions was integrated into a central database. Researchers can select which information for the genes within a candidate interval or for single genes shall be displayed. Genes can also interactively be filtered, sorted and prioritised according to criteria derived from the background knowledge and preconception of the disease under scrutiny. CONCLUSIONS: GeneDistiller provides knowledge-driven, fully interactive and intuitive access to multiple data sources. It displays maximum relevant information, while saving the user from drowning in the flood of data. A typical query takes less than two seconds, thus allowing an interactive and explorative approach to the hunt for the candidate gene. ACCESS: GeneDistiller can be freely accessed at http://www.genedistiller.org.

  2. RANGE: Gene Transfer of Reversibly Controlled Polycistronic Genes

    Directory of Open Access Journals (Sweden)

    Yiwei Chen

    2013-01-01

    Full Text Available We developed a single vector recombinant adeno-associated viral (rAAV expression system for spatial and reversible control of polycistronic gene expression. Our approach (i integrates the advantages of the tetracycline (Tet-controlled transcriptional silencer tTSKid and the self-cleaving 2A peptide bridge, (ii combines essential regulatory components as an autoregulatory loop, (iii simplifies the gene delivery scheme, and (iv regulates multiple genes in a synchronized manner. Controlled by an upstream Tet-responsive element (TRE, both the ubiquitous chicken β-actin promoter (CAG and the neuron-specific synapsin-1 promoter (Syn could regulate expression of tTSKid together with two 2A-linked reporter genes. Transduction in vitro exhibited maximally 50-fold regulation by doxycycline (Dox. Determined by gene delivery method as well as promoter, highly specific tissues were transduced in vivo. Bioluminescence imaging (BLI visualized reversible “ON/OFF” gene switches over repeated “Doxy-Cycling” in living mice. Thus, the reversible rAAV-mediated N-cistronic gene expression system, termed RANGE, may serve as a versatile tool to achieve reversible polycistronic gene regulation for the study of gene function as well as gene therapy.

  3. RANGE: Gene Transfer of Reversibly Controlled Polycistronic Genes.

    Science.gov (United States)

    Chen, Yiwei; Cao, Liji; Luo, Chonglin; Ditzel, Désirée Aw; Peter, Jörg; Sprengel, Rolf

    2013-04-09

    We developed a single vector recombinant adeno-associated viral (rAAV) expression system for spatial and reversible control of polycistronic gene expression. Our approach (i) integrates the advantages of the tetracycline (Tet)-controlled transcriptional silencer tTS(Kid) and the self-cleaving 2A peptide bridge, (ii) combines essential regulatory components as an autoregulatory loop, (iii) simplifies the gene delivery scheme, and (iv) regulates multiple genes in a synchronized manner. Controlled by an upstream Tet-responsive element (TRE), both the ubiquitous chicken β-actin promoter (CAG) and the neuron-specific synapsin-1 promoter (Syn) could regulate expression of tTS(Kid) together with two 2A-linked reporter genes. Transduction in vitro exhibited maximally 50-fold regulation by doxycycline (Dox). Determined by gene delivery method as well as promoter, highly specific tissues were transduced in vivo. Bioluminescence imaging (BLI) visualized reversible "ON/OFF" gene switches over repeated "Doxy-Cycling" in living mice. Thus, the reversible rAAV-mediated N-cistronic gene expression system, termed RANGE, may serve as a versatile tool to achieve reversible polycistronic gene regulation for the study of gene function as well as gene therapy.Molecular Therapy - Nucleic Acids (2013) 2, e85; doi:10.1038/mtna.2013.15; published online 9 April 2013.

  4. Genes, Children and Pediatricians

    Directory of Open Access Journals (Sweden)

    Joana Correia

    2017-01-01

    Full Text Available A male newborn, presenting hipotonia and posterior parietal bossing, developed, in the first 12 hours of life, refusal to feed and hypoglycaemia. A cranial ultrasound, skull X-ray and CT scan revealed an occipital and parietal fracture with an underlying haematoma and extensive extracranial soft-tissue swelling. He was submitted to surgical drainage. After 24 hours: new intracerebral bleeding. At the age of two-months he presented abnormal skin and sparse kinky hair. Serum copper and caeruloplasmin levels were below the normal range. Molecular diagnosis of Menkes disease was made by the identification of a new mutation in ATP7A gene.

  5. MUTATIONS IN CALMODULIN GENES

    DEFF Research Database (Denmark)

    2013-01-01

    The present invention relates to an isolated polynucleotide encoding at least a part of calmodulin and an isolated polypeptide comprising at least a part of a calmodulin protein, wherein the polynucleotide and the polypeptide comprise at least one mutation associated with a cardiac disorder. The ...... the binding of calmodulin to ryanodine receptor 2 and use of such compound in a treatment of an individual having a cardiac disorder. The invention further provides a kit that can be used to detect specific mutations in calmodulin encoding genes....

  6. MUTATIONS IN CALMODULIN GENES

    DEFF Research Database (Denmark)

    2013-01-01

    The present invention relates to an isolated polynucleotide encoding at least a part of calmodulin and an isolated polypeptide comprising at least a part of a calmodulin protein, wherein the polynucleotide and the polypeptide comprise at least one mutation associated with a cardiac disorder...... the binding of calmodulin to ryanodine receptor 2 and use of such compound in a treatment of an individual having a cardiac disorder. The invention further provides a kit that can be used to detect specific mutations in calmodulin encoding genes....

  7. Genes and Disease: Prader-Willi Syndrome

    Science.gov (United States)

    ... MD): National Center for Biotechnology Information (US); 1998-. Genes and Disease [Internet]. Show details National Center for ... 45K) PDF version of this title (3.8M) Gene sequence Genome view see gene locations Entrez Gene ...

  8. Determination of single-nucleotide polymorphism in the proximal promoter region of apolipoprotein M gene in coronary artery diseases

    Directory of Open Access Journals (Sweden)

    Lu Zheng

    2009-09-01

    Full Text Available Lu Zheng1, Guanghua Luo1, Xiaoying Zhang1, Jun Zhang1, Jiang Zhu1, Jiang Wei1, Qinfeng Mu1, Lujun Chen1, Peter Nilsson-Ehle2, Ning Xu21Comprehensive Laboratory, The Third Affiliated Hospital, Suzhou University, Changzhou China; 2Division of Clinical Chemistry and Pharmacology, Department of Laboratory Medicine, Lund University, Lund, SwedenObjective: It has been reported that single-nucleotide polymorphism (SNP in the proximal promoter region of apolipoprotein M (apoM gene may confer the risk in the development of type 2 diabetes (T2D and coronary artery disease (CAD in the Han Chinese. However, in a recent study demonstrated that plasma apoM level did not correlated to the coronary heart disease. In the present studies, we investigated the SNP T-778C of apoM gene in CAD patients and controls in the Han Chinese population. Moreover we examined whether serum apoM levels could be influenced by this promoter mutation.Material and methods: One hundred twenty-six CAD patients and 118 non-CAD patients were subjected in the present study. All patients were confirmed by the angiography. The genotyping of polymorphisms T-778C in apoM promoter was determined by real-time polymerase chain reaction. Serum apoM levels were semi-quantitatively determined by the dot-blotting analysis. Results: Distribution of apoM T-778C genotype in non-CAD patients was as following: 84.7% were T/T, 15.3% were T/C and 0.0% was C/C. T allele frequencies were 92.4% and C allele, 7.6%. In the CAD patients, 99 patients (78.6% had the T/T genotype, 25 patients (19.8% with T/C genotype and 2 patients (1.6% with C/C genotype. The allele frequency was 88.5% for the T allele and 11.5% for the C allele. There was no statistical significant difference of serum apoM levels found in these three genotypes.Conclusions: There was no significant difference in allele or genotype frequencies between CAD patients and non-CAD patients. Binary logistic regression analysis with adjustments for age

  9. 不同日粮模式对奶山羊乳成分和乳腺中脂肪合成相关基因表达的影响研究%Effects of Different Model Diets on Milk Composition and Expression of Genes Related to Fatty Acid Synthesis in Mammary Gland of Lactating Dairy Goats

    Institute of Scientific and Technical Information of China (English)

    张航; 敖长金; 哈斯额尔敦; 宋利文; 张兴夫

    2016-01-01

    The current study determined the effects of two diets with different forage profiles on milk composition and the expression of key genes associated with fatty acid synthesis in the mammary gland of lactating dairy goats. Eight multiparous lactating goats (BW = 45.6 ± 2.5 kg, days in milk = 90 ± 12 d) fitted with external pudic artery (EPA) and subskin abdominal vein (SAV) intubations were assigned to two treatments in a crossover design. Animals were fed diets with different roughage profiles with the concentrate-roughage ratio in the treatments being 40:60. Diets were:(1) a high quality roughage treatment (HCA) containing 30% Chinese wildrye hay, 20% corn silage, 10% alfalfa and 40% concentrate (CP: 10.6%, NDF: 50.4% and ME: 2.24 Mcal/kg).(2) a low quality roughage treatment (HCS) containing 30% Chinese wildrye hay, 30% corn stover and 40% concentrate (CP: 14.2%, NDF: 39.7% and ME: 2.39 Mcal/kg), on dry matter (DM) basis. Each period lasted 21 d. The first 18 d served as an adaptation period, followed by a 3 d sample collection period. Dry matter intake (DMI) and milk yield and milk composition were measured. Milk and blood samples from EPA and SAV were collected for fatty acid (FA) analysis. Mammary gland biopsies were performed after milking on the last day of each period and the tissues were analyzed for mRNA expression of acetyl-coenzyme A carboxylase- α (ACACA), fatty acid synthesis (FASN), stearoyl CoA desaturase (SCD), and lipoprotein lipase (LPL). Milk yield was lower in HCA than HCS (496.5 vs. 515.5 g/d). Milk fat content was significantly higher in HCA than in HCS (3.16% vs. 2.96%).Milk protein content was higher in HCA than in HCS (2.99% vs. 2.89%). Milk fatty acid composition had no significant changed between HCA and HCS except for C18:3 (0.27 vs. 0.15 g/100g), which was significantly different. Compared with HCS, HCA had an increase in subskin abdominal vein (SAV) plasma concentration of total fatty acids (0.62 vs. 0.44 mg/mL). No differences

  10. Alcoholism: genes and mechanisms.

    Science.gov (United States)

    Oroszi, Gabor; Goldman, David

    2004-12-01

    Alcoholism is a chronic relapsing/remitting disease that is frequently unrecognized and untreated, in part because of the partial efficacy of treatment. Only approximately one-third of patients remain abstinent and one-third have fully relapsed 1 year after withdrawal from alcohol, with treated patients doing substantially better than untreated [1]. The partial effectiveness of strategies for prevention and treatment, and variation in clinical course and side effects, represent a challenge and an opportunity to better understand the neurobiology of addiction. The strong heritability of alcoholism suggests the existence of inherited functional variants of genes that alter the metabolism of alcohol and variants of other genes that alter the neurobiologies of reward, executive cognitive function, anxiety/dysphoria, and neuronal plasticity. Each of these neurobiologies has been identified as a critical domain in the addictions. Functional alleles that alter alcoholism-related intermediate phenotypes include common alcohol dehydrogenase 1B and aldehyde dehydrogenase 2 variants that cause the aversive flushing reaction; catechol-O-methyltransferase (COMT) Val158Met leading to differences in three aspects of neurobiology: executive cognitive function, stress/anxiety response, and opioid function; opioid receptor micro1 (OPRM1) Asn40Asp, which may serve as a gatekeeper molecule in the action of naltrexone, a drug used in alcoholism treatment; and HTTLPR, which alters serotonin transporter function and appears to affect stress response and anxiety/dysphoria, which are factors relevant to initial vulnerability, the process of addiction, and relapse.

  11. Tetraspanin genes in plants.

    Science.gov (United States)

    Wang, Feng; Vandepoele, Klaas; Van Lijsebettens, Mieke

    2012-07-01

    Tetraspanins represent a four-transmembrane protein superfamily with a conserved structure and amino acid residues that are present in mammals, insects, fungi and plants. Tetraspanins interact with each other or with other membrane proteins to form tetraspanin-enriched microdomains that play important roles in development, pathogenesis and immune responses via facilitating cell-cell adhesion and fusion, ligand binding and intracellular trafficking. Here, we emphasize evolutionary aspects within the plant kingdom based on genomic sequence information. A phylogenetic tree based on 155 tetraspanin genes of 11 plant species revealed ancient and fast evolving clades. Tetraspanins were only present in multicellular plants, were often duplicated in the plant genomes and predicted by the electronic Fluorescent Pictograph for gene expression analysis to be either functionally redundant or divergent. Tetraspanins contain a large extracellular loop with conserved cysteines that provide the binding sites for the interactions. The Arabidopsis thaliana TETRASPANIN1/TORNADO2/EKEKO has a function in leaf and root patterning and TETRASPANIN3 was identified in the plasmodesmatal proteome, suggesting a role in cell-cell communication during plant development.

  12. Improvements to cardiovascular gene ontology.

    Science.gov (United States)

    Lovering, Ruth C; Dimmer, Emily C; Talmud, Philippa J

    2009-07-01

    Gene Ontology (GO) provides a controlled vocabulary to describe the attributes of genes and gene products in any organism. Although one might initially wonder what relevance a 'controlled vocabulary' might have for cardiovascular science, such a resource is proving highly useful for researchers investigating complex cardiovascular disease phenotypes as well as those interpreting results from high-throughput methodologies. GO enables the current functional knowledge of individual genes to be used to annotate genomic or proteomic datasets. In this way, the GO data provides a very effective way of linking biological knowledge with the analysis of the large datasets of post-genomics research. Consequently, users of high-throughput methodologies such as expression arrays or proteomics will be the main beneficiaries of such annotation sets. However, as GO annotations increase in quality and quantity, groups using small-scale approaches will gradually begin to benefit too. For example, genome wide association scans for coronary heart disease are identifying novel genes, with previously unknown connections to cardiovascular processes, and the comprehensive annotation of these novel genes might provide clues to their cardiovascular link. At least 4000 genes, to date, have been implicated in cardiovascular processes and an initiative is underway to focus on annotating these genes for the benefit of the cardiovascular community. In this article we review the current uses of Gene Ontology annotation to highlight why Gene Ontology should be of interest to all those involved in cardiovascular research.

  13. Chromatin analysis of occluded genes

    Science.gov (United States)

    Lee, Jae Hyun; Gaetz, Jedidiah; Bugarija, Branimir; Fernandes, Croydon J.; Snyder, Gregory E.; Bush, Eliot C.; Lahn, Bruce T.

    2009-01-01

    We recently described two opposing states of transcriptional competency. One is termed ‘competent’ whereby a gene is capable of responding to trans-acting transcription factors of the cell, such that it is active if appropriate transcriptional activators are present, though it can also be silent if activators are absent or repressors are present. The other is termed ‘occluded’ whereby a gene is silenced by cis-acting, chromatin-based mechanisms in a manner that blocks it from responding to trans-acting factors, such that it is silent even when activators are present in the cellular milieu. We proposed that gene occlusion is a mechanism by which differentiated cells stably maintain their phenotypic identities. Here, we describe chromatin analysis of occluded genes. We found that DNA methylation plays a causal role in maintaining occlusion for a subset of occluded genes. We further examined a variety of other chromatin marks typically associated with transcriptional silencing, including histone variants, covalent histone modifications and chromatin-associated proteins. Surprisingly, we found that although many of these marks are robustly linked to silent genes (which include both occluded genes and genes that are competent but silent), none is linked specifically to occluded genes. Although the observation does not rule out a possible causal role of these chromatin marks in occlusion, it does suggest that these marks might be secondary effect rather than primary cause of the silent state in many genes. PMID:19380460

  14. Molecular characterization of Iranian patients with possible familial hypercholesterolemia.

    Science.gov (United States)

    Farrokhi, E; Shayesteh, F; Asadi Mobarakeh, S; Roghani Dehkordi, F; Ghatreh Samani, K; Hashemzadeh Chaleshtori, M

    2011-07-01

    Familial hypercholesterolemia (FH) is an autosomal dominant disorder of lipoprotein metabolism caused mainly by mutations in the low-density lipoprotein receptor (LDLR) and apolipoprotein B 100 (APOB) genes. Until now, the molecular basis of FH has been demonstrated in detail in many populations, but there is still very limited Molecular data concerning FH in Iran. The aim of this study was to characterize the LDLR and APOB gene mutations in an Iranian population. A total of 30 non-related Iranian possible FH subjects were studied. Diagnosis of FH was based on the Dutch Lipid Clinic Network diagnostic criteria. All samples were initially tested for three common APOB gene mutations including R3500Q, R3500 W and R3531C using PCR-RFLP assay. Subsequently, promoter and coding region of the LDLR gene was screened by PCR-SSCP analysis and positive results were confirmed by DNA sequencing. Four previously reported polymorphisms 1413G > A, 1725C > T, 1773T > C and 2140 + 5G > A were found in ~17% (5/30) of population studied. Moreover, no variation was found in APOB gene. Our data indicated that LDLR and APOB gene mutations have not contribution to possible FH in Iranian population studied here. However, we examined three common APOB mutations and LDLR in only 30 patients, and to determine the role of these genes in developing FH in Iran, more FH samples and populations needed to be investigated for the mutations of the related genes.

  15. Identification of genes and gene products necessary for bacterial bioluminescence.

    OpenAIRE

    Engebrecht, J; Silverman, M.

    1984-01-01

    Expression of luminescence in Escherichia coli was recently achieved by cloning genes from the marine bacterium Vibrio fischeri. One DNA fragment on a hybrid plasmid encoded regulatory functions and enzymatic activities necessary for light production. We report the results of a genetic analysis to identify the luminescence genes (lux) that reside on this recombinant plasmid. lux gene mutations were generated by hydroxylamine treatment, and these mutations were ordered on a linear map by compl...

  16. GENE MUTATIONS, GENETIC DISEASE AND PHARMACOGENETIC GENES DISORDER

    OpenAIRE

    Ishak

    2010-01-01

    Somatic cell mutation is able to create genetic variance in a cell population and can induce cancer and tumor when gene mutations took place at repressor gene in controlling cell cycles such as p53 gene. Whereas germline cell mutation can cause genetic disease such as sickle cell anemia, breast cancer, thalassemia, parkinson’s as well as defect of biochemical pathway that influence drug-receptor interaction, which has negative effect and lead to hospitalized of patient. Most of reports mentio...

  17. PROAPOPTOTIC FUNCTION OF FHIT GENE

    Institute of Scientific and Technical Information of China (English)

    QIU Zhe-fu; HAN De-min; ZHANG Luo; ZHANG Wei

    2006-01-01

    Tumor suppressor gene plays an important role in maintaining the homeostasis between cell loss and growth. Fragile in maintaining the homeostasis between cell loss and growth. Fragile histidine triad (FHIT) gene found recently was studied in a deep going way; it becomes the focus as a result of its roleof ep going way; it becomes the focus as a result of its roleof anti-tumor in human various type of tissue. Due to the high efficiency of FHIT gene benefiting the anti-tumor, it is proposed gh efficiency of FHIT gene benefiting the anti-tumor, it is proposed as a candidate of tumor suppressor gene though there are several opposite opinions.several opposite opinions. We stress the summary of some properties of FHIT gene on proapoptosis according to the published data which showed gene on proapoptosis according to the published data which showed the stronger proapoptotic function of FHIT gene; the apoptosis induced by FHIT depends on the expression level and status of ene; the apoptosis induced by FHIT depends on the expression level and status of FHIT; and FHIT gene can alternate the cell cycling properties and reduce the tumorigenic potential; the apoptotic process e can alternate the cell cycling properties and reduce the tumorigenic potential; the apoptotic process induced by FHIT has no relation to p53 gene. In a ward, in consideration of its multiple functions against malignancies, FHIT in consideration of its multiple functions against malignancies, FHIT gene deserves attention and exploration as a selective target for searching the mechanism of tumorigenesis and clinical et for searching the mechanism of tumorigenesis and clinical therapeutic applications in further.le histidine triad (FHIT) gene; Apoptosis; Tumorigenesis; Tumor suppressor gene deserves attention and exploration as a selective target for searching the mechanism of tumorigenesis and clinical therapeutic applications in further.

  18. Regulation of gene expression by Goodwin's loop with many genes

    Science.gov (United States)

    Sielewiesiuk, Jan; Łopaciuk, Agata

    2012-01-01

    The paper presents a simple analysis of a long Goodwin's loop containing many genes. The genes form a closed series. The rate of transcription of any gene is up or down regulated by theprotein product of the preceding gene. We describe the loop with a system of ordinary differential equations of order s. Oscillatory solutions of the system are possible at the odd number of repressions and any number of inductions if the product of all Hill's coefficients, related to both repressions and inductions, is larger than:

  19. Gene: a gene-centered information resource at NCBI.

    Science.gov (United States)

    Brown, Garth R; Hem, Vichet; Katz, Kenneth S; Ovetsky, Michael; Wallin, Craig; Ermolaeva, Olga; Tolstoy, Igor; Tatusova, Tatiana; Pruitt, Kim D; Maglott, Donna R; Murphy, Terence D

    2015-01-01

    The National Center for Biotechnology Information's (NCBI) Gene database (www.ncbi.nlm.nih.gov/gene) integrates gene-specific information from multiple data sources. NCBI Reference Sequence (RefSeq) genomes for viruses, prokaryotes and eukaryotes are the primary foundation for Gene records in that they form the critical association between sequence and a tracked gene upon which additional functional and descriptive content is anchored. Additional content is integrated based on the genomic location and RefSeq transcript and protein sequence data. The content of a Gene record represents the integration of curation and automated processing from RefSeq, collaborating model organism databases, consortia such as Gene Ontology, and other databases within NCBI. Records in Gene are assigned unique, tracked integers as identifiers. The content (citations, nomenclature, genomic location, gene products and their attributes, phenotypes, sequences, interactions, variation details, maps, expression, homologs, protein domains and external databases) is available via interactive browsing through NCBI's Entrez system, via NCBI's Entrez programming utilities (E-Utilities and Entrez Direct) and for bulk transfer by FTP.

  20. Gene expression analysis identifies global gene dosage sensitivity in cancer

    DEFF Research Database (Denmark)

    Fehrmann, Rudolf S. N.; Karjalainen, Juha M.; Krajewska, Malgorzata;

    2015-01-01

    expression. We reanalyzed 77,840 expression profiles and observed a limited set of 'transcriptional components' that describe well-known biology, explain the vast majority of variation in gene expression and enable us to predict the biological function of genes. On correcting expression profiles...... for these components, we observed that the residual expression levels (in 'functional genomic mRNA' profiling) correlated strongly with copy number. DNA copy number correlated positively with expression levels for 99% of all abundantly expressed human genes, indicating global gene dosage sensitivity. By applying...

  1. PDMAEMA based gene delivery materials

    Directory of Open Access Journals (Sweden)

    Seema Agarwal

    2012-09-01

    Full Text Available Gene transfection is the transfer of genetic material like DNA into cells. Cationic polymers which form nanocomplexes with DNA, so-called non-viral gene vectors, are a highly promising platform for efficient gene transfection. Despite intensive research efforts and some of the on-going clinical trials on gene transfection, none of the existing cationic polymer systems are generally acceptable for human gene therapy. Since the process of gene transfection is complex and puts different challenges and demands on the delivery system, there is a strong requirement for the design and development of a multifunctional system in a simple way. This review will discuss recent efforts in design, synthesis, and performance of poly(2-dimethylaminoethyl methacrylate (PDMAEMA nanocomplexes with DNA.

  2. Gene targeting with retroviral vectors

    Energy Technology Data Exchange (ETDEWEB)

    Ellis, J.; Bernstein, A. (Toronto Univ., ON (Canada))

    1989-04-01

    The authors have designed and constructed integration-defective retroviral vectors to explore their potential for gene targeting in mammalian cells. Two nonoverlapping deletion mutants of the bacterial neomycin resistance (neo) gene were used to detect homologous recombination events between viral and chromosomal sequences. Stable neo gene correction events were selected at a frequency of approximately 1 G418/sup r/ cell per 3 x 10/sup 6/ infected cells. Analysis of the functional neo gene in independent targeted cell clones indicated that unintegrated retroviral linear DNA recombined with the target by gene conversion for variable distances into regions of nonhomology. In addition, transient neo gene correction events which were associated with the complete loss of the chromosomal target sequences were observed. These results demonstrated that retroviral vectors can recombine with homologous chromosomal sequences in rodent and human cells.

  3. Brief isoflurane anaesthesia affects differential gene expression, gene ontology and gene networks in rat brain.

    Science.gov (United States)

    Lowes, Damon A; Galley, Helen F; Moura, Alessandro P S; Webster, Nigel R

    2017-01-15

    Much is still unknown about the mechanisms of effects of even brief anaesthesia on the brain and previous studies have simply compared differential expression profiles with and without anaesthesia. We hypothesised that network analysis, in addition to the traditional differential gene expression and ontology analysis, would enable identification of the effects of anaesthesia on interactions between genes. Rats (n=10 per group) were randomised to anaesthesia with isoflurane in oxygen or oxygen only for 15min, and 6h later brains were removed. Differential gene expression and gene ontology analysis of microarray data was performed. Standard clustering techniques and principal component analysis with Bayesian rules were used along with social network analysis methods, to quantitatively model and describe the gene networks. Anaesthesia had marked effects on genes in the brain with differential regulation of 416 probe sets by at least 2 fold. Gene ontology analysis showed 23 genes were functionally related to the anaesthesia and of these, 12 were involved with neurotransmitter release, transport and secretion. Gene network analysis revealed much greater connectivity in genes from brains from anaesthetised rats compared to controls. Other importance measures were also altered after anaesthesia; median [range] closeness centrality (shortest path) was lower in anaesthetized animals (0.07 [0-0.30]) than controls (0.39 [0.30-0.53], pgenes after anaesthesia and suggests future targets for investigation. Copyright © 2016 Elsevier B.V. All rights reserved.

  4. How eukaryotic genes are transcribed

    OpenAIRE

    Venters, Bryan J; Pugh, B. Franklin

    2009-01-01

    Regulation of eukaryotic gene expression is far more complex than one might have imagined thirty years ago. However, progress towards understanding gene regulatory mechanisms has been rapid and comprehensive, which has made the integration of detailed observations into broadly connected concepts a challenge. This review attempts to integrate the following concepts: 1) a well-defined organization of nucleosomes and modification states at most genes, 2) regulatory networks of sequence-specific ...

  5. Gene set analysis for GWAS

    DEFF Research Database (Denmark)

    Debrabant, Birgit; Soerensen, Mette

    2014-01-01

    Abstract We discuss the use of modified Kolmogorov-Smirnov (KS) statistics in the context of gene set analysis and review corresponding null and alternative hypotheses. Especially, we show that, when enhancing the impact of highly significant genes in the calculation of the test statistic...... parameter and the genesis and distribution of the gene-level statistics, and illustrate the effects of differential weighting in a real-life example....

  6. Gene and genome parameters of mammalian liver circadian genes (LCGs.

    Directory of Open Access Journals (Sweden)

    Gang Wu

    Full Text Available The mammalian circadian system controls various physiology processes and behavior responses by regulating thousands of circadian genes with rhythmic expressions. In this study, we redefined circadian-regulated genes based on published results in the mouse liver and compared them with other gene groups defined relative to circadian regulations, especially the non-circadian-regulated genes expressed in liver at multiple molecular levels from gene position to protein expression based on integrative analyses of different datasets from the literature. Based on the intra-tissue analysis, the liver circadian genes or LCGs show unique features when compared to other gene groups. First, LCGs in general have less neighboring genes and larger in both genomic and 3'-UTR lengths but shorter in CDS (coding sequence lengths. Second, LCGs have higher mRNA and protein abundance, higher temporal expression variations, and shorter mRNA half-life. Third, more than 60% of LCGs form major co-expression clusters centered in four temporal windows: dawn, day, dusk, and night. In addition, larger and smaller LCGs are found mainly expressed in the day and night temporal windows, respectively, and we believe that LCGs are well-partitioned into the gene expression regulatory network that takes advantage of gene size, expression constraint, and chromosomal architecture. Based on inter-tissue analysis, more than half of LCGs are ubiquitously expressed in multiple tissues but only show rhythmical expression in one or limited number of tissues. LCGs show at least three-fold lower expression variations across the temporal windows than those among different tissues, and this observation suggests that temporal expression variations regulated by the circadian system is relatively subtle as compared with the tissue expression variations formed during development. Taken together, we suggest that the circadian system selects gene parameters in a cost effective way to improve tissue

  7. Testing for gene-gene interaction with AMMI models.

    Science.gov (United States)

    Barhdadi, Amina; Dubé, Marie-Pierre

    2010-01-01

    Studies have shown that many common diseases are influenced by multiple genes and their interactions. There is currently a strong interest in testing for association between combinations of these genes and disease, in particular because genes that affect the risk of disease only in the presence of another genetic variant may not be detected in marginal analysis. In this paper we propose the use of additive main effect and multiplicative interaction (AMMI) models to detect and to quantify gene-gene interaction effects for a quantitative trait. The objective of the present research is to demonstrate the practical advantages of these models to describe complex interaction between two unlinked loci. Although gene-gene interactions have often been defined as a deviance from additive genetic effects, the residual term has generally not been appropriately treated. The AMMI models allow for the analysis of a two way factorial data structure and combine the analysis of variance of the two main genotype effects with a principal component analysis of the residual multiplicative interaction. The AMMI models for gene-gene interaction presented here allow for the testing of non additivity between the two loci, and also describe how their interaction structure fits the existing non-additivity. Moreover, these models can be used to identify the specific two genotypes combinations that contribute to the significant gene-gene interaction. We describe the use of the biplot to display the structure of the interaction and evaluate the performance of the AMMI and the special cases of the AMMI previously described by Tukey and Mandel with simulated data sets. Our simulated study showed that the AMMI model is as powerful as general linear models when the interaction is not modeled in the presence of marginal effects. However, in the presence of pure epitasis, i.e. in the absence of marginal effects, the AMMI method was not found to be superior to other tested regression methods.

  8. Introduction: Cancer Gene Networks.

    Science.gov (United States)

    Clarke, Robert

    2017-01-01

    Constructing, evaluating, and interpreting gene networks generally sits within the broader field of systems biology, which continues to emerge rapidly, particular with respect to its application to understanding the complexity of signaling in the context of cancer biology. For the purposes of this volume, we take a broad definition of systems biology. Considering an organism or disease within an organism as a system, systems biology is the study of the integrated and coordinated interactions of the network(s) of genes, their variants both natural and mutated (e.g., polymorphisms, rearrangements, alternate splicing, mutations), their proteins and isoforms, and the organic and inorganic molecules with which they interact, to execute the biochemical reactions (e.g., as enzymes, substrates, products) that reflect the function of that system. Central to systems biology, and perhaps the only approach that can effectively manage the complexity of such systems, is the building of quantitative multiscale predictive models. The predictions of the models can vary substantially depending on the nature of the model and its inputoutput relationships. For example, a model may predict the outcome of a specific molecular reaction(s), a cellular phenotype (e.g., alive, dead, growth arrest, proliferation, and motility), a change in the respective prevalence of cell or subpopulations, a patient or patient subgroup outcome(s). Such models necessarily require computers. Computational modeling can be thought of as using machine learning and related tools to integrate the very high dimensional data generated from modern, high throughput omics technologies including genomics (next generation sequencing), transcriptomics (gene expression microarrays; RNAseq), metabolomics and proteomics (ultra high performance liquid chromatography, mass spectrometry), and "subomic" technologies to study the kinome, methylome, and others. Mathematical modeling can be thought of as the use of ordinary

  9. Genes, evolution and intelligence.

    Science.gov (United States)

    Bouchard, Thomas J

    2014-11-01

    I argue that the g factor meets the fundamental criteria of a scientific construct more fully than any other conception of intelligence. I briefly discuss the evidence regarding the relationship of brain size to intelligence. A review of a large body of evidence demonstrates that there is a g factor in a wide range of species and that, in the species studied, it relates to brain size and is heritable. These findings suggest that many species have evolved a general-purpose mechanism (a general biological intelligence) for dealing with the environments in which they evolved. In spite of numerous studies with considerable statistical power, we know of very few genes that influence g and the effects are very small. Nevertheless, g appears to be highly polygenic. Given the complexity of the human brain, it is not surprising that that one of its primary faculties-intelligence-is best explained by the near infinitesimal model of quantitative genetics.

  10. Gene-environment interaction.

    Science.gov (United States)

    Manuck, Stephen B; McCaffery, Jeanne M

    2014-01-01

    With the advent of increasingly accessible technologies for typing genetic variation, studies of gene-environment (G×E) interactions have proliferated in psychological research. Among the aims of such studies are testing developmental hypotheses and models of the etiology of behavioral disorders, defining boundaries of genetic and environmental influences, and identifying individuals most susceptible to risk exposures or most amenable to preventive and therapeutic interventions. This research also coincides with the emergence of unanticipated difficulties in detecting genetic variants of direct association with behavioral traits and disorders, which may be obscured if genetic effects are expressed only in predisposing environments. In this essay we consider these and other rationales for positing G×E interactions, review conceptual models meant to inform G×E interpretations from a psychological perspective, discuss points of common critique to which G×E research is vulnerable, and address the role of the environment in G×E interactions.

  11. Angiogenin gene polymorphism

    Institute of Scientific and Technical Information of China (English)

    Hongli Wang; Dongsheng Fan; Yingshuang Zhang

    2013-01-01

    Angiogenin is associated with the pathogenesis of diabetic peripheral neuropathy. Here, we se-quenced the coding region of the angiogenin gene in genomic DNA from 207 patients with type 2 diabetes mel itus (129 diabetic peripheral neuropathy patients and 78 diabetic non-neuropathy pa-tients) and 268 healthy controls. Al subjects were from the Han population of northern China. No mutations were found. We then compared the genotype and allele frequencies of the angiogenin synonymous single nucleotide polymorphism rs11701 between the diabetic peripheral neuropathy patients and controls, and between the diabetic neuropathy and non-neuropathy patients, using a case-control design. We detected no statistical y significant genetic associations. Angiogenin may not be associated with genetic susceptibility to diabetic peripheral neuropathy in the Han population of northern China.

  12. Gene therapy in the cornea.

    Science.gov (United States)

    Mohan, Rajiv R; Sharma, Ajay; Netto, Marcelo V; Sinha, Sunilima; Wilson, Steven E

    2005-09-01

    Technological advances in the field of gene therapy has prompted more than three hundred phase I and phase II gene-based clinical trials for the treatment of cancer, AIDS, macular degeneration, cardiovascular, and other monogenic diseases. Besides treating diseases, gene transfer technology has been utilized for the development of preventive and therapeutic vaccines for malaria, tuberculosis, hepatitis A, B and C viruses, AIDS, and influenza. The potential therapeutic applications of gene transfer technology are enormous. The cornea is an excellent candidate for gene therapy because of its accessibility and immune-privileged nature. In the last two decades, various viral vectors, such as adeno, adeno-associated, retro, lenti, and herpes simplex, as well as non-viral methods, were examined for introducing DNA into corneal cells in vitro, in vivo and ex vivo. Most of these studies used fluorescent or non-fluorescent marker genes to track the level and duration of transgene expression in corneal cells. However, limited studies were directed to evaluate prospects of gene-based interventions for corneal diseases or disorders such as allograft rejection, laser-induced post-operative haze, herpes simplex keratitis, and wound healing in animal models. We will review the successes and obstacles impeding gene therapy approaches used for delivering genes into the cornea.

  13. Are TMEM genes potential candidate genes for panic disorder?

    DEFF Research Database (Denmark)

    Gregersen, Noomi O; Buttenschøn, Henriette Nørmølle; Hedemand, Anne

    2014-01-01

    We analysed single nucleotide polymorphisms in two transmembrane genes (TMEM98 and TMEM132E) in panic disorder (PD) patients and control individuals from the Faroe Islands, Denmark and Germany. The genes encode single-pass membrane proteins and are located within chromosome 17q11.2-q12...

  14. Gene-gene Interaction Analyses for Atrial Fibrillation

    NARCIS (Netherlands)

    Lin, Honghuang; Mueller-Nurasyid, Martina; Smith, Albert V; Arking, Dan E; Barnard, John; Bartz, Traci M; Lunetta, Kathryn L; Lohman, Kurt; Kleber, Marcus E; Lubitz, Steven A; Geelhoed, Bastiaan; Trompet, Stella; Niemeijer, Maartje N; Kacprowski, Tim; Chasman, Daniel I; Klarin, Derek; Sinner, Moritz F; Waldenberger, Melanie; Meitinger, Thomas; Harris, Tamara B; Launer, Lenore J; Soliman, Elsayed Z; Chen, Lin Y; Smith, Jonathan D; Van Wagoner, David R; Rotter, Jerome I; Psaty, Bruce M; Xie, Zhijun; Hendricks, Audrey E; Ding, Jingzhong; Delgado, Graciela E; Verweij, Niek; van der Harst, Pim; Macfarlane, Peter W; Ford, Ian; Hofman, Albert; Uitterlinden, André; Heeringa, Jan; Franco, Oscar H; Kors, Jan A; Weiss, Stefan; Völzke, Henry; Rose, Lynda M; Natarajan, Pradeep; Kathiresan, Sekar; Kääb, Stefan; Gudnason, Vilmundur; Alonso, Alvaro; Chung, Mina K; Heckbert, Susan R; Benjamin, Emelia J; Liu, Yongmei; März, Winfried; Rienstra, Michiel; Jukema, J Wouter; Stricker, Bruno H; Dörr, Marcus; Albert, Christine M; Ellinor, Patrick T

    2016-01-01

    Atrial fibrillation (AF) is a heritable disease that affects more than thirty million individuals worldwide. Extensive efforts have been devoted to the study of genetic determinants of AF. The objective of our study is to examine the effect of gene-gene interaction on AF susceptibility. We performed

  15. Gene-gene Interaction Analyses for Atrial Fibrillation

    NARCIS (Netherlands)

    H. Lin (Honghuang); M. Mueller-Nurasyid; A.V. Smith (Albert Vernon); D.E. Arking (Dan); J. Barnard (John); T.M. Bartz (Traci M.); K.L. Lunetta (Kathryn); K. Lohman (Kurt); M.E. Kleber (Marcus); S.A. Lubitz (Steven); Geelhoed, B. (Bastiaan); S. Trompet (Stella); M.N. Niemeijer (Maartje); T. Kacprowski (Tim); D.I. Chasman (Daniel); Klarin, D. (Derek); M.F. Sinner (Moritz); M. Waldenberger (Melanie); T. Meitinger (Thomas); T.B. Harris (Tamara); Launer, L.J. (Lenore J.); E.Z. Soliman (Elsayed Z.); L. Chen (Lin); J.D. Smith (Jonathan); D.R. van Wagoner (David); Rotter, J.I. (Jerome I.); B.M. Psaty (Bruce); Xie, Z. (Zhijun); A.E. Hendricks (Audrey E.); Ding, J. (Jingzhong); G.E. Delgado (Graciela E.); N. Verweij (Niek); P. van der Harst (Pim); P.W. MacFarlane (Peter); I. Ford (Ian); A. Hofman (Albert); A.G. Uitterlinden (André); J. Heeringa (Jan); O.H. Franco (Oscar); J.A. Kors (Jan); Weiss, S. (Stefan); H. Völzke (Henry); L.M. Rose (Lynda); Natarajan, P. (Pradeep); S. Kathiresan (Sekar); S. Kääb (Stefan); V. Gudnason (Vilmundur); A. Alonso (Alvaro); M.K. Chung (Mina); S.R. Heckbert (Susan); E.J. Benjamin (Emelia); Y. Liu (Yongmei); W. März (Winfried); S.A. Rienstra; J.W. Jukema (Jan Wouter); B.H.Ch. Stricker (Bruno); M. Dörr (Marcus); C.M. Albert (Christine); P.T. Ellinor (Patrick)

    2016-01-01

    textabstractAtrial fibrillation (AF) is a heritable disease that affects more than thirty million individuals worldwide. Extensive efforts have been devoted to the study of genetic determinants of AF. The objective of our study is to examine the effect of gene-gene interaction on AF susceptibility.

  16. Classifying genes to the correct Gene Ontology Slim term in Saccharomyces cerevisiae using neighbouring genes with classification learning

    Directory of Open Access Journals (Sweden)

    Tsatsoulis Costas

    2010-05-01

    Full Text Available Abstract Background There is increasing evidence that gene location and surrounding genes influence the functionality of genes in the eukaryotic genome. Knowing the Gene Ontology Slim terms associated with a gene gives us insight into a gene's functionality by informing us how its gene product behaves in a cellular context using three different ontologies: molecular function, biological process, and cellular component. In this study, we analyzed if we could classify a gene in Saccharomyces cerevisiae to its correct Gene Ontology Slim term using information about its location in the genome and information from its nearest-neighbouring genes using classification learning. Results We performed experiments to establish that the MultiBoostAB algorithm using the J48 classifier could correctly classify Gene Ontology Slim terms of a gene given information regarding the gene's location and information from its nearest-neighbouring genes for training. Different neighbourhood sizes were examined to determine how many nearest neighbours should be included around each gene to provide better classification rules. Our results show that by just incorporating neighbour information from each gene's two-nearest neighbours, the percentage of correctly classified genes to their correct Gene Ontology Slim term for each ontology reaches over 80% with high accuracy (reflected in F-measures over 0.80 of the classification rules produced. Conclusions We confirmed that in classifying genes to their correct Gene Ontology Slim term, the inclusion of neighbour information from those genes is beneficial. Knowing the location of a gene and the Gene Ontology Slim information from neighbouring genes gives us insight into that gene's functionality. This benefit is seen by just including information from a gene's two-nearest neighbouring genes.

  17. Classifying genes to the correct Gene Ontology Slim term in Saccharomyces cerevisiae using neighbouring genes with classification learning.

    Science.gov (United States)

    Amthauer, Heather A; Tsatsoulis, Costas

    2010-05-28

    There is increasing evidence that gene location and surrounding genes influence the functionality of genes in the eukaryotic genome. Knowing the Gene Ontology Slim terms associated with a gene gives us insight into a gene's functionality by informing us how its gene product behaves in a cellular context using three different ontologies: molecular function, biological process, and cellular component. In this study, we analyzed if we could classify a gene in Saccharomyces cerevisiae to its correct Gene Ontology Slim term using information about its location in the genome and information from its nearest-neighbouring genes using classification learning. We performed experiments to establish that the MultiBoostAB algorithm using the J48 classifier could correctly classify Gene Ontology Slim terms of a gene given information regarding the gene's location and information from its nearest-neighbouring genes for training. Different neighbourhood sizes were examined to determine how many nearest neighbours should be included around each gene to provide better classification rules. Our results show that by just incorporating neighbour information from each gene's two-nearest neighbours, the percentage of correctly classified genes to their correct Gene Ontology Slim term for each ontology reaches over 80% with high accuracy (reflected in F-measures over 0.80) of the classification rules produced. We confirmed that in classifying genes to their correct Gene Ontology Slim term, the inclusion of neighbour information from those genes is beneficial. Knowing the location of a gene and the Gene Ontology Slim information from neighbouring genes gives us insight into that gene's functionality. This benefit is seen by just including information from a gene's two-nearest neighbouring genes.

  18. On meme--gene coevolution.

    Science.gov (United States)

    Bull, L; Holland, O; Blackmore, S

    2000-01-01

    In this article we examine the effects of the emergence of a new replicator, memes, on the evolution of a pre-existing replicator, genes. Using a version of the NKCS model we examine the effects of increasing the rate of meme evolution in relation to the rate of gene evolution, for various degrees of interdependence between the two replicators. That is, the effects of memes' (suggested) more rapid rate of evolution in comparison to that of genes is investigated using a tunable model of coevolution. It is found that, for almost any degree of interdependence between the two replicators, as the rate of meme evolution increases, a phase transition-like dynamic occurs under which memes have a significantly detrimental effect on the evolution of genes, quickly resulting in the cessation of effective gene evolution. Conversely, the memes experience a sharp increase in benefit from increasing their rate of evolution. We then examine the effects of enabling genes to reduce the percentage of gene-detrimental evolutionary steps taken by memes. Here a critical region emerges as the comparative rate of meme evolution increases, such that if genes cannot effectively select memes a high percentage of the time, they suffer from meme evolution as if they had almost no selective capability.

  19. Susceptibility Genes in Thyroid Autoimmunity

    Directory of Open Access Journals (Sweden)

    Yoshiyuki Ban

    2005-01-01

    Full Text Available The autoimmune thyroid diseases (AITD are complex diseases which are caused by an interaction between susceptibility genes and environmental triggers. Genetic susceptibility in combination with external factors (e.g. dietary iodine is believed to initiate the autoimmune response to thyroid antigens. Abundant epidemiological data, including family and twin studies, point to a strong genetic influence on the development of AITD. Various techniques have been employed to identify the genes contributing to the etiology of AITD, including candidate gene analysis and whole genome screening. These studies have enabled the identification of several loci (genetic regions that are linked with AITD, and in some of these loci, putative AITD susceptibility genes have been identified. Some of these genes/loci are unique to Graves' disease (GD and Hashimoto's thyroiditis (HT and some are common to both the diseases, indicating that there is a shared genetic susceptibility to GD and HT. The putative GD and HT susceptibility genes include both immune modifying genes (e.g. HLA, CTLA-4 and thyroid specific genes (e.g. TSHR, Tg. Most likely, these loci interact and their interactions may influence disease phenotype and severity.

  20. The flow of gene expression.

    Science.gov (United States)

    Misteli, Tom

    2004-03-01

    Gene expression is a highly interconnected multistep process. A recent meeting in Iguazu Falls, Argentina, highlighted the need to uncover both the molecular details of each single step as well as the mechanisms of coordination among processes in order to fully understand the expression of genes.

  1. Phytochrome-regulated Gene Expression

    Institute of Scientific and Technical Information of China (English)

    Peter H. Quail

    2007-01-01

    Identification of all genes involved in the phytochrome (phy)-mediated responses of plants to their light environment is an important goal in providing an overall understanding of light-regulated growth and development. This article highlights and integrates the central findings of two recent comprehensive studies in Arabidopsis that have identified the genome-wide set of phy-regulated genes that respond rapidly to red-light signals upon first exposure of dark-grown seedlings, and have tested the functional relevance to normal seedling photomorphogenesis of an initial subset of these genes. The data: (a) reveal considerable complexity in the channeling of the light signals through the different phy-family members (phyA to phyE) to responsive genes; (b) identify a diversity of transcription-factor-encoding genes as major early, if not primary, targets of phy signaling, and, therefore, as potentially important regulators in the transcriptional-network hierarchy; and (c) identify auxin-related genes as the dominant class among rapidly-regulated, hormone-related genes. However, reverse-genetic functional profiling of a selected subset of these genes reveals that only a limited fraction are necessary for optimal phy-induced seedling deetiolation.

  2. Candidate genes for behavioural ecology

    NARCIS (Netherlands)

    Fitzpatrick, M.J.; Ben-Sahar, Y.; Smid, H.M.; Vet, L.E.M.; Robinson, G.E.; Sokolowski, M.B.

    2005-01-01

    In spite of millions of years of evolutionary divergence, the conservation of gene function is common across distant lineages. As such, genes that are known to influence behaviour in one organism are likely to influence similar behaviours in other organisms. Recent studies of the evolution of behavi

  3. Candidate gene prioritization with Endeavour.

    Science.gov (United States)

    Tranchevent, Léon-Charles; Ardeshirdavani, Amin; ElShal, Sarah; Alcaide, Daniel; Aerts, Jan; Auboeuf, Didier; Moreau, Yves

    2016-07-08

    Genomic studies and high-throughput experiments often produce large lists of candidate genes among which only a small fraction are truly relevant to the disease, phenotype or biological process of interest. Gene prioritization tackles this problem by ranking candidate genes by profiling candidates across multiple genomic data sources and integrating this heterogeneous information into a global ranking. We describe an extended version of our gene prioritization method, Endeavour, now available for six species and integrating 75 data sources. The performance (Area Under the Curve) of Endeavour on cross-validation benchmarks using 'gold standard' gene sets varies from 88% (for human phenotypes) to 95% (for worm gene function). In addition, we have also validated our approach using a time-stamped benchmark derived from the Human Phenotype Ontology, which provides a setting close to prospective validation. With this benchmark, using 3854 novel gene-phenotype associations, we observe a performance of 82%. Altogether, our results indicate that this extended version of Endeavour efficiently prioritizes candidate genes. The Endeavour web server is freely available at https://endeavour.esat.kuleuven.be/.

  4. Determining Semantically Related Significant Genes.

    Science.gov (United States)

    Taha, Kamal

    2014-01-01

    GO relation embodies some aspects of existence dependency. If GO term xis existence-dependent on GO term y, the presence of y implies the presence of x. Therefore, the genes annotated with the function of the GO term y are usually functionally and semantically related to the genes annotated with the function of the GO term x. A large number of gene set enrichment analysis methods have been developed in recent years for analyzing gene sets enrichment. However, most of these methods overlook the structural dependencies between GO terms in GO graph by not considering the concept of existence dependency. We propose in this paper a biological search engine called RSGSearch that identifies enriched sets of genes annotated with different functions using the concept of existence dependency. We observe that GO term xcannot be existence-dependent on GO term y, if x- and y- have the same specificity (biological characteristics). After encoding into a numeric format the contributions of GO terms annotating target genes to the semantics of their lowest common ancestors (LCAs), RSGSearch uses microarray experiment to identify the most significant LCA that annotates the result genes. We evaluated RSGSearch experimentally and compared it with five gene set enrichment systems. Results showed marked improvement.

  5. Nonviral Vectors for Gene Delivery

    Science.gov (United States)

    Baoum, Abdulgader Ahmed

    2011-12-01

    The development of nonviral vectors for safe and efficient gene delivery has been gaining considerable attention recently. An ideal nonviral vector must protect the gene against degradation by nuclease in the extracellular matrix, internalize the plasma membrane, escape from the endosomal compartment, unpackage the gene at some point and have no detrimental effects. In comparison to viruses, nonviral vectors are relatively easy to synthesize, less immunogenic, low in cost, and have no limitation in the size of a gene that can be delivered. Significant progress has been made in the basic science and applications of various nonviral gene delivery vectors; however, the majority of nonviral approaches are still inefficient and often toxic. To this end, two nonviral gene delivery systems using either biodegradable poly(D,L-lactide- co-glycolide) (PLG) nanoparticles or cell penetrating peptide (CPP) complexes have been designed and studied using A549 human lung epithelial cells. PLG nanoparticles were optimized for gene delivery by varying particle surface chemistry using different coating materials that adsorb to the particle surface during formation. A variety of cationic coating materials were studied and compared to more conventional surfactants used for PLG nanoparticle fabrication. Nanoparticles (˜200 nm) efficiently encapsulated plasmids encoding for luciferase (80-90%) and slowly released the same for two weeks. After a delay, moderate levels of gene expression appeared at day 5 for certain positively charged PLG particles and gene expression was maintained for at least two weeks. In contrast, gene expression mediated by polyethyleneimine (PEI) ended at day 5. PLG particles were also significantly less cytotoxic than PEI suggesting the use of these vehicles for localized, sustained gene delivery to the pulmonary epithelium. On the other hand, a more simple method to synthesize 50-200 nm complexes capable of high transfection efficiency or high gene knockdown was

  6. Delivery systems for gene therapy

    Directory of Open Access Journals (Sweden)

    Shrikant Mali

    2013-01-01

    Full Text Available The structure of DNA was unraveled by Watson and Crick in 1953, and two decades later Arber, Nathans and Smith discovered DNA restriction enzymes, which led to the rapid growth in the field of recombinant DNA technology. From expressing cloned genes in bacteria to expressing foreign DNA in transgenic animals, DNA is now slated to be used as a therapeutic agent to replace defective genes in patients suffering from genetic disorders or to kill tumor cells in cancer patients. Gene therapy provides modern medicine with new perspectives that were unthinkable two decades ago. Progress in molecular biology and especially, molecular medicine is now changing the basics of clinical medicine. A variety of viral and non-viral possibilities are available for basic and clinical research. This review summarizes the delivery routes and methods for gene transfer used in gene therapy.

  7. Function analysis of unknown genes

    DEFF Research Database (Denmark)

    Rogowska-Wrzesinska, A.

    2002-01-01

      This thesis entitled "Function analysis of unknown genes" presents the use of proteome analysis for the characterisation of yeast (Saccharomyces cerevisiae) genes and their products (proteins especially those of unknown function). This study illustrates that proteome analysis can be used...... to describe different aspects of molecular biology of the cell, to study changes that occur in the cell due to overexpression or deletion of a gene and to identify various protein modifications. The biological questions and the results of the described studies show the diversity of the information that can...... genes and proteins. It reports the first global proteome database collecting 36 yeast single gene deletion mutants and selecting over 650 differences between analysed mutants and the wild type strain. The obtained results show that two-dimensional gel electrophoresis and mass spectrometry based proteome...

  8. Nanoparticles for retinal gene therapy.

    Science.gov (United States)

    Conley, Shannon M; Naash, Muna I

    2010-09-01

    Ocular gene therapy is becoming a well-established field. Viral gene therapies for the treatment of Leber's congentinal amaurosis (LCA) are in clinical trials, and many other gene therapy approaches are being rapidly developed for application to diverse ophthalmic pathologies. Of late, development of non-viral gene therapies has been an area of intense focus and one technology, polymer-compacted DNA nanoparticles, is especially promising. However, development of pharmaceutically and clinically viable therapeutics depends not only on having an effective and safe vector but also on a practical treatment strategy. Inherited retinal pathologies are caused by mutations in over 220 genes, some of which contain over 200 individual disease-causing mutations, which are individually very rare. This review will focus on both the progress and future of nanoparticles and also on what will be required to make them relevant ocular pharmaceutics. Copyright 2010 Elsevier Ltd. All rights reserved.

  9. Gene targeting in malaria parasites.

    Science.gov (United States)

    Ménard, R; Janse, C

    1997-10-01

    Gene targeting, which permits alteration of a chosen gene in a predetermined way by homologous recombination, is an emerging technology in malaria research. Soon after the development of techniques for stable transformation of red blood cell stages of Plasmodium falciparum and Plasmodium berghei, genes of interest were disrupted in the two species. The main limitations of gene targeting in malaria parasites result from the intracellular growth and slow replication of these parasites. On the other hand, the technology is facilitated by the very high rate of homologous recombination following transformation with targeting constructs (approximately 100%). Here, we describe (i) the vector design and the type of mutation that may be generated in a target locus, (ii) the selection and screening strategies that can be used to identify clones with the desired modification, and (iii) the protocol that was used for disrupting the circumsporozoite protein (CS) and thrombospondin-related anonymous protein (TRAP) genes of P. berghei.

  10. Gene expression profiling: can we identify the right target genes?

    Directory of Open Access Journals (Sweden)

    J. E. Loyd

    2008-12-01

    Full Text Available Gene expression profiling allows the simultaneous monitoring of the transcriptional behaviour of thousands of genes, which may potentially be involved in disease development. Several studies have been performed in idiopathic pulmonary fibrosis (IPF, which aim to define genetic links to the disease in an attempt to improve the current understanding of the underlying pathogenesis of the disease and target pathways for intervention. Expression profiling has shown a clear difference in gene expression between IPF and normal lung tissue, and has identified a wide range of candidate genes, including those known to encode for proteins involved in extracellular matrix formation and degradation, growth factors and chemokines. Recently, familial pulmonary fibrosis cohorts have been examined in an attempt to detect specific genetic mutations associated with IPF. To date, these studies have identified families in which IPF is associated with mutations in the gene encoding surfactant protein C, or with mutations in genes encoding components of telomerase. Although rare and clearly not responsible for the disease in all individuals, the nature of these mutations highlight the importance of the alveolar epithelium in disease pathogenesis and demonstrate the potential for gene expression profiling in helping to advance the current understanding of idiopathic pulmonary fibrosis.

  11. Genes, Economics, and Happiness *

    Science.gov (United States)

    De Neve, Jan-Emmanuel; Christakis, Nicholas A.; Fowler, James H.; Frey, Bruno S.

    2012-01-01

    We explore the influence of genetic variation on subjective well-being by employing a twin design and genetic association study. In a nationally-representative twin sample, we first show that about 33% of the variation in life satisfaction is explained by genetic variation. Although previous studies have shown that baseline happiness is significantly heritable, little research has considered molecular genetic associations with subjective well-being. We study the relationship between a functional polymorphism on the serotonin transporter gene (5-HTTLPR) and life satisfaction. We initially find that individuals with the longer, transcriptionally more efficient variant of this genotype report greater life satisfaction (n=2,545, p=0.012). However, our replication attempts on independent samples produce mixed results indicating that more work needs to be done to better understand the relationship between this genotype and subjective well-being. This work has implications for how economists think about the determinants of utility, and the extent to which exogenous shocks might affect individual well-being. PMID:24349601

  12. Genes, Economics, and Happiness.

    Science.gov (United States)

    De Neve, Jan-Emmanuel; Christakis, Nicholas A; Fowler, James H; Frey, Bruno S

    2012-11-01

    We explore the influence of genetic variation on subjective well-being by employing a twin design and genetic association study. In a nationally-representative twin sample, we first show that about 33% of the variation in life satisfaction is explained by genetic variation. Although previous studies have shown that baseline happiness is significantly heritable, little research has considered molecular genetic associations with subjective well-being. We study the relationship between a functional polymorphism on the serotonin transporter gene (5-HTTLPR) and life satisfaction. We initially find that individuals with the longer, transcriptionally more efficient variant of this genotype report greater life satisfaction (n=2,545, p=0.012). However, our replication attempts on independent samples produce mixed results indicating that more work needs to be done to better understand the relationship between this genotype and subjective well-being. This work has implications for how economists think about the determinants of utility, and the extent to which exogenous shocks might affect individual well-being.

  13. Gene Prediction Using Multinomial Probit Regression with Bayesian Gene Selection

    Directory of Open Access Journals (Sweden)

    Xiaodong Wang

    2004-01-01

    Full Text Available A critical issue for the construction of genetic regulatory networks is the identification of network topology from data. In the context of deterministic and probabilistic Boolean networks, as well as their extension to multilevel quantization, this issue is related to the more general problem of expression prediction in which we want to find small subsets of genes to be used as predictors of target genes. Given some maximum number of predictors to be used, a full search of all possible predictor sets is combinatorially prohibitive except for small predictors sets, and even then, may require supercomputing. Hence, suboptimal approaches to finding predictor sets and network topologies are desirable. This paper considers Bayesian variable selection for prediction using a multinomial probit regression model with data augmentation to turn the multinomial problem into a sequence of smoothing problems. There are multiple regression equations and we want to select the same strongest genes for all regression equations to constitute a target predictor set or, in the context of a genetic network, the dependency set for the target. The probit regressor is approximated as a linear combination of the genes and a Gibbs sampler is employed to find the strongest genes. Numerical techniques to speed up the computation are discussed. After finding the strongest genes, we predict the target gene based on the strongest genes, with the coefficient of determination being used to measure predictor accuracy. Using malignant melanoma microarray data, we compare two predictor models, the estimated probit regressors themselves and the optimal full-logic predictor based on the selected strongest genes, and we compare these to optimal prediction without feature selection.

  14. Therapeutic genes for anti-HIV/AIDS gene therapy.

    Science.gov (United States)

    Bovolenta, Chiara; Porcellini, Simona; Alberici, Luca

    2013-01-01

    The multiple therapeutic approaches developed so far to cope HIV-1 infection, such as anti-retroviral drugs, germicides and several attempts of therapeutic vaccination have provided significant amelioration in terms of life-quality and survival rate of AIDS patients. Nevertheless, no approach has demonstrated efficacy in eradicating this lethal, if untreated, infection. The curative power of gene therapy has been proven for the treatment of monogenic immunodeficiensies, where permanent gene modification of host cells is sufficient to correct the defect for life-time. No doubt, a similar concept is not applicable for gene therapy of infectious immunodeficiensies as AIDS, where there is not a single gene to be corrected; rather engineered cells must gain immunotherapeutic or antiviral features to grant either short- or long-term efficacy mostly by acquisition of antiviral genes or payloads. Anti-HIV/AIDS gene therapy is one of the most promising strategy, although challenging, to eradicate HIV-1 infection. In fact, genetic modification of hematopoietic stem cells with one or multiple therapeutic genes is expected to originate blood cell progenies resistant to viral infection and thereby able to prevail on infected unprotected cells. Ultimately, protected cells will re-establish a functional immune system able to control HIV-1 replication. More than hundred gene therapy clinical trials against AIDS employing different viral vectors and transgenes have been approved or are currently ongoing worldwide. This review will overview anti-HIV-1 infection gene therapy field evaluating strength and weakness of the transgenes and payloads used in the past and of those potentially exploitable in the future.

  15. Progress of gene targeting in mouse

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    Gene targeting is a powerful approach of study- ing the genefunction in vivo. Specific genetic modifications, including simple gene disruption, point mutations, large chromosomal deletions and rearrangements, targeted incor- poration of foreign genes, could be introduced into the mouse genome by gene targeting. Recent studies make it possible to do the gene targeting with temporal and spatial control.

  16. Apolipoprotein A5 and lipoprotein lipase interact to modulate anthropometric measures in Hispanics of Caribbean origin

    Science.gov (United States)

    Apolipoprotein A5 (APOA5) and lipoprotein lipase (LPL) proteins interact functionally to regulate lipid metabolism, and single nucleotide polymorphisms (SNPs) for each gene have also been associated independently with obesity risk. Evaluating gene combinations may be more effective than single SNP a...

  17. Human Lacrimal Gland Gene Expression

    Science.gov (United States)

    Aakalu, Vinay Kumar; Parameswaran, Sowmya; Maienschein-Cline, Mark; Bahroos, Neil; Shah, Dhara; Ali, Marwan; Krishnakumar, Subramanian

    2017-01-01

    Background The study of human lacrimal gland biology and development is limited. Lacrimal gland tissue is damaged or poorly functional in a number of disease states including dry eye disease. Development of cell based therapies for lacrimal gland diseases requires a better understanding of the gene expression and signaling pathways in lacrimal gland. Differential gene expression analysis between lacrimal gland and other embryologically similar tissues may be helpful in furthering our understanding of lacrimal gland development. Methods We performed global gene expression analysis of human lacrimal gland tissue using Affymetrix ® gene expression arrays. Primary data from our laboratory was compared with datasets available in the NLM GEO database for other surface ectodermal tissues including salivary gland, skin, conjunctiva and corneal epithelium. Results The analysis revealed statistically significant difference in the gene expression of lacrimal gland tissue compared to other ectodermal tissues. The lacrimal gland specific, cell surface secretory protein encoding genes and critical signaling pathways which distinguish lacrimal gland from other ectodermal tissues are described. Conclusions Differential gene expression in human lacrimal gland compared with other ectodermal tissue types revealed interesting patterns which may serve as the basis for future studies in directed differentiation among other areas. PMID:28081151

  18. Comprehensive resource: Skeletal gene database.

    Science.gov (United States)

    Jia, L; Ho, N C; Park, S S; Powell, J; Francomano, C A

    2001-01-01

    The Skeletal Gene Database (SGD) is an integrated resource that provides comprehensive information about bone-related genes, mRNA, and proteins expressed in human and mouse, with rich links to numerous other electronic tools. SGD contains expressed sequence tag (EST) data from all the skeletal-related cDNA libraries that are available to the public. It supplies the query/data access analytic tools for users to search and compare each gene expressed in skeletal tissue(s). The results derived from EST tissue expression profiling will allow users to get the data on the mRNA copy numbers of each gene expressed in each tissue and its normalized value. From the SGD, researchers can obtain information regarding the name, symbol, size, exon/intron number, chromosomal location, LocusLink, and related disease (if any is known) of each gene. This electronic compendium also furnishes information on the protein of the corresponding gene including the protein size (amino acid number and molecular weight). It provides swift and ready access to other useful databases including OMIM, UniGene and PUBMED. The data will be updated regularly in step with current and future research, thereby providing what we hope will serve as a highly useful source of information and a powerful analytic tool to the scientific community.

  19. GENES IN SPORT AND DOPING

    Directory of Open Access Journals (Sweden)

    Andrzej Pokrywka

    2013-06-01

    Full Text Available Genes control biological processes such as muscle production of energy, mitochondria biogenesis, bone formation erythropoiesis, angiogenesis, vasodilation, neurogenesis, etc. DNA profiling for athletes reveals genetic variations that may be associated with endurance ability, muscle performance and power exercise, tendon susceptibility to injuries and psychological aptitude. Already, over 200 genes relating to physical performance have been identified by several research groups. Athletes’ genotyping is developing as a tool for the formulation of personalized training and nutritional programmes to optimize sport training as well as for the prediction of exercise-related injuries. On the other hand, development of molecular technology and gene therapy creates a risk of non-therapeutic use of cells, genes and genetic elements to improve athletic performance. Therefore, the World Anti-Doping Agency decided to include prohibition of gene doping within their World Anti-Doping Code in 2003. In this review article, we will provide a current overview of genes for use in athletes’ genotyping and gene doping possibilities, including their development and detection techniques.

  20. Approaches for skeletal gene therapy.

    Science.gov (United States)

    Niyibizi, Christopher; Wallach, Corey J; Mi, Zhibao; Robbins, Paul D

    2002-01-01

    The role of gene therapy in the treatment of musculoskeletal disorders continues to be an active area of research. As the etiology of many musculoskeletal diseases becomes increasingly understood, advances in cellular and gene therapy maybe applied to their potential treatment This review focuses on current investigational strategies to treat osteogenesis imperfecta (OI). OI is a varied group of genetic disorders that result in the diminished integrity of connective tissues as a result of alterations in the genes that encode for either the pro alpha1 or pro alpha2 component of type I collagen. Because most forms of OI result from dominant negative mutations, isolated gene replacement therapy is not a logical treatment option. The combined use of genetic manipulation and cellular transplantation, however, may provide a means to overcome this obstacle. This article describes the recent laboratory and clinical advances in cell therapy, highlights potential techniques being investigated to suppress the expression of the mutant allele with antisense gene therapy, and attempts to deliver collagen genes to bone cells. The challenges that the investigators face in their quest for the skeletal gene therapy are also discussed.

  1. Linking Genes to Cardiovascular Diseases: Gene Action and Gene-Environment Interactions.

    Science.gov (United States)

    Pasipoularides, Ares

    2015-12-01

    A unique myocardial characteristic is its ability to grow/remodel in order to adapt; this is determined partly by genes and partly by the environment and the milieu intérieur. In the "post-genomic" era, a need is emerging to elucidate the physiologic functions of myocardial genes, as well as potential adaptive and maladaptive modulations induced by environmental/epigenetic factors. Genome sequencing and analysis advances have become exponential lately, with escalation of our knowledge concerning sometimes controversial genetic underpinnings of cardiovascular diseases. Current technologies can identify candidate genes variously involved in diverse normal/abnormal morphomechanical phenotypes, and offer insights into multiple genetic factors implicated in complex cardiovascular syndromes. The expression profiles of thousands of genes are regularly ascertained under diverse conditions. Global analyses of gene expression levels are useful for cataloging genes and correlated phenotypes, and for elucidating the role of genes in maladies. Comparative expression of gene networks coupled to complex disorders can contribute insights as to how "modifier genes" influence the expressed phenotypes. Increasingly, a more comprehensive and detailed systematic understanding of genetic abnormalities underlying, for example, various genetic cardiomyopathies is emerging. Implementing genomic findings in cardiology practice may well lead directly to better diagnosing and therapeutics. There is currently evolving a strong appreciation for the value of studying gene anomalies, and doing so in a non-disjointed, cohesive manner. However, it is challenging for many-practitioners and investigators-to comprehend, interpret, and utilize the clinically increasingly accessible and affordable cardiovascular genomics studies. This survey addresses the need for fundamental understanding in this vital area.

  2. Viral vectors for gene transfer: current status of gene therapeutics.

    Science.gov (United States)

    Heilbronn, Regine; Weger, Stefan

    2010-01-01

    Gene therapy for the correction of inherited or acquired disease has gained increasing importance in recent years. Successful treatment of children suffering from severe combined immunodeficiency (SCID) was achieved using retrovirus vectors for gene transfer. Encouraging improvements of vision were reported in a genetic eye disorder (LCA) leading to early childhood blindness. Adeno-associated virus (AAV) vectors were used for gene transfer in these trials. This chapter gives an overview of the design and delivery of viral vectors for the transport of a therapeutic gene into a target cell or tissue. The construction and production of retrovirus, lentivirus, and AAV vectors are covered. The focus is on production methods suitable for biopharmaceutical upscaling and for downstream processing. Quality control measures and biological safety considerations for the use of vectors in clinical trials are discussed.

  3. [Pathogenicity and pneumococcal capsular genes].

    Science.gov (United States)

    García, E; García, P; López, R

    1994-01-01

    Pneumococci remain to be one of the most prominent human pathogens. Increasing efforts are being dedicated to the development of improved vaccines with wider specificity. Since a clear understanding of the genetics of capsular types in Streptococcus pneumoniae is missing, our efforts are oriented to characterize, at the molecular level, the genes involved in capsular polysaccharide biosynthesis. We have cloned and sequenced a chromosomal DNA fragment of a clinical isolate of type 3 pneumococcus and showed that it contains a type 3 specific gene as well as genes common to other serotypes.

  4. Panspermia and horizontal gene transfer

    Science.gov (United States)

    Klyce, Brig

    2009-08-01

    Evidence that extremophiles are hardy and ubiquitous is helping to make panspermia a respectable theory. But even if life on Earth originally came from space, biologists assume that the subsequent evolution of life is still governed by the darwinian paradigm. In this review we show how panspermia could amend darwinism and point to a cosmic source for, not only extremophiles but, all of life. This version of panspermia can be called "strong panspermia." To support this theory we will discuss recent evidence pertaining to horizontal gene transfer, viruses, genes apparently older than the Earthly evolution of the features they encode, and primate-specific genes without identifiable precursors.

  5. Familial Hypobetalipoproteinemia-Induced Nonalcoholic Steatohepatitis

    Directory of Open Access Journals (Sweden)

    Mindy C.W. Lam

    2012-07-01

    Full Text Available Familial hypobetalipoproteinemia (FHBL is a rare genetic disorder of lipid metabolism that is associated with abnormally low serum levels of low-density lipoprotein (LDL cholesterol and apolipoprotein B. It is an autosomal co-dominant disorder, and depending on zygosity, the clinical manifestations may vary from none to neurological, endocrine, hematological or liver dysfunction. Nonalcoholic fatty liver disease is common in persons with FHBL, however progression to nonalcoholic steatohepatitis is unusual. We describe here a patient with a novel APOB mutation, V703I, which appears to contribute to the severity of the FHBL phenotype. He had liver enzyme abnormalities, increased echogenicity of the liver consistent with steatosis, very low LDL cholesterol at 0.24 mmol/l (normal 1.8–3.5 mmol/l and an extremely low apolipoprotein B level of 0.16 g/l (normal 0.6–1.2 g/l. APOB gene sequencing revealed him to be a compound heterozygote with two mutations (R463W and V703I. APOB R463W has previously been reported to cause FHBL. Genetic sequencing of his first-degree relatives identified the APOB V703I mutation in his normolipidemic brother and father and the APOB R463W mutation in his mother and sister, both of whom have very low LDL cholesterol levels. These results suggest that the APOB V703I mutation alone does not cause the FHBL phenotype. However, it is possible that it has a contributory role to a more aggressive phenotype in the presence of APOB R463W.

  6. Fattigdomens hjälplöshet – too hot to handle? Hur Astrid Lindgrens böcker om Madicken översatts i USA och Storbritannien

    Directory of Open Access Journals (Sweden)

    Nikolowski-Bogomoloff, Angelika

    2011-03-01

    Full Text Available In children’s literature, power relations are fundamentally assymetrical. This is furthermore accentuated in the process of translation where translation norms, social and cultural norms as well as the power game of adult authorities play a major part.The Swedish author Astrid Lindgren’s ideology is based on the notion that no aspects of life should be hidden from the child, making her thematize as well as break taboos in her writing for children. There has been extensive research on Lindgren’s authorship per se, but research on translations of her books seems to be limited. The fact that discussions on taboo elements in children’s books in general, and Lindgren’s source texts and target texts in particular are sparse indicates that this is a vast – and interesting – field still to be explored.This paper focuses on the American and British translations of Lindgren’s Madicken (1960 and Madicken och Junibackens Pims (1976 in order to find out why and to what extent these books were censored in translation.

  7. The Gene Ontology (GO) project in 2006

    National Research Council Canada - National Science Library

    2006-01-01

    The Gene Ontology (GO) project (http://www.geneontology.org) develops and uses a set of structured, controlled vocabularies for community use in annotating genes, gene products and sequences (also see http://song.sourceforge.net...

  8. The Gene Ontology project in 2008

    National Research Council Canada - National Science Library

    The Gene Ontology (GO) project (http://www.geneontology.org/) provides a set of structured, controlled vocabularies for community use in annotating genes, gene products and sequences (also see http://www.sequenceontology.org...

  9. Integrating Gene Ontology and Blast to predict gene functions

    Institute of Scientific and Technical Information of China (English)

    WANG Cheng-gang; MO Zhi-hong

    2007-01-01

    A GoBlast system was built to predict gene function by integrating Blast search and Gene Ontology (GO) annotations together. The operation system was based on Debian Linux 3.1, with Apache as the web server and Mysql database as the data storage system. FASTA files with GO annotations were taken as the sequence source for blast alignment, which were formatted by wu-formatdb program. The GoBlast system includes three Bioperl modules in Perl: a data input module, a data process module and a data output module. A GoBlast query starts with an amino acid or nucleotide sequence. It ends with an output in an html page, presenting high scoring gene products which are of a high homology to the queried sequence and listing associated GO terms beside respective gene poducts. A simple click on a GO term leads to the detailed explanation of the specific gene function. This avails gene function prediction by Blast. GoBlast can be a very useful tool for functional genome research and is available for free at http://bioq.org/goblast.

  10. Gene function prediction based on the Gene Ontology hierarchical structure.

    Science.gov (United States)

    Cheng, Liangxi; Lin, Hongfei; Hu, Yuncui; Wang, Jian; Yang, Zhihao

    2014-01-01

    The information of the Gene Ontology annotation is helpful in the explanation of life science phenomena, and can provide great support for the research of the biomedical field. The use of the Gene Ontology is gradually affecting the way people store and understand bioinformatic data. To facilitate the prediction of gene functions with the aid of text mining methods and existing resources, we transform it into a multi-label top-down classification problem and develop a method that uses the hierarchical relationships in the Gene Ontology structure to relieve the quantitative imbalance of positive and negative training samples. Meanwhile the method enhances the discriminating ability of classifiers by retaining and highlighting the key training samples. Additionally, the top-down classifier based on a tree structure takes the relationship of target classes into consideration and thus solves the incompatibility between the classification results and the Gene Ontology structure. Our experiment on the Gene Ontology annotation corpus achieves an F-value performance of 50.7% (precision: 52.7% recall: 48.9%). The experimental results demonstrate that when the size of training set is small, it can be expanded via topological propagation of associated documents between the parent and child nodes in the tree structure. The top-down classification model applies to the set of texts in an ontology structure or with a hierarchical relationship.

  11. How eukaryotic genes are transcribed.

    Science.gov (United States)

    Venters, Bryan J; Pugh, B Franklin

    2009-06-01

    Regulation of eukaryotic gene expression is far more complex than one might have imagined 30 years ago. However, progress towards understanding gene regulatory mechanisms has been rapid and comprehensive, which has made the integration of detailed observations into broadly connected concepts a challenge. This review attempts to integrate the following concepts: (1) a well-defined organization of nucleosomes and modification states at most genes; (2) regulatory networks of sequence-specific transcription factors; (3) chromatin remodeling coupled to promoter assembly of the general transcription factors and RNA polymerase II; and (4) phosphorylation states of RNA polymerase II coupled to chromatin modification states during transcription. The wealth of new insights arising from the tools of biochemistry, genomics, cell biology, and genetics is providing a remarkable view into the mechanics of gene regulation.

  12. Gene Variants Reduce Opioid Risks

    Science.gov (United States)

    ... Opioids Prescription Drugs & Cold Medicines Steroids (Anabolic) Synthetic Cannabinoids (K2/Spice) Synthetic Cathinones (Bath Salts) Tobacco/Nicotine ... variant of the gene for the μ-opioid receptor (OPRM1) with a decreased risk for addiction to ...

  13. Gene therapy in ocular diseases

    Directory of Open Access Journals (Sweden)

    Singh Vijay

    2002-01-01

    Full Text Available Gene therapy is a novel form of drug delivery that enlists the synthetic machinery of the patient′s cells to produce a therapeutic agent. Genes may be delivered into cells in vi