Dataset Information

Genetic studies on the APOA1-C3-A5 gene cluster in Asian Indians with premature coronary artery disease.

ABSTRACT: The APOA1-C3-A5 gene cluster plays an important role in the regulation of lipids. Asian Indians have an increased tendency for abnormal lipid levels and high risk of Coronary Artery Disease (CAD). Therefore, the present study aimed to elucidate the relationship of four single nucleotide polymorphisms (SNPs) in the Apo11q cluster, namely the -75G>A, +83C>T SNPs in the APOA1 gene, the Sac1 SNP in the APOC3 gene and the S19W variant in the APOA5 gene to plasma lipids and CAD in 190 affected sibling pairs (ASPs) belonging to Asian Indian families with a strong CAD history.Genotyping and lipid assays were carried out using standard protocols. Plasma lipids showed a strong heritability (h2 48% - 70%; P < 0.0001). A subset of 77 ASPs with positive sign of Logarithm of Odds (LOD) score showed significant linkage to CAD trait by multi-point analysis (LOD score 7.42, P < 0.001) and to Sac1 (LOD score 4.49) and -75G>A (LOD score 2.77) SNPs by single-point analysis (P < 0.001). There was significant proportion of mean allele sharing (pi) for the Sac1 (pi 0.59), -75G>A (pi 0.56) and +83C>T (pi 0.52) (P < 0.001) SNPs, respectively. QTL analysis showed suggestive evidence of linkage of the Sac1 SNP to Total Cholesterol (TC), High Density Lipoprotein-cholesterol (HDL-C) and Apolipoprotein B (ApoB) with LOD scores of 1.42, 1.72 and 1.19, respectively (P < 0.01). The Sac1 and -75G>A SNPs along with hypertension showed maximized correlations with TC, TG and Apo B by association analysis.The APOC3-Sac1 SNP is an important genetic variant that is associated with CAD through its interaction with plasma lipids and other standard risk factors among Asian Indians.

SUBMITTER: Shanker J

PROVIDER: S-EPMC2556320 | biostudies-literature | 2008 Sep

REPOSITORIES: biostudies-literature

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Genetic studies on the APOA1-C3-A5 gene cluster in Asian Indians with premature coronary artery disease.

Shanker Jayashree J Perumal Ganapathy G Rao Veena S VS Khadrinarasimhiah Natesha B NB John Shibu S Hebbagodi Sridhara S Mukherjee Manjari M Kakkar Vijay V VV

Lipids in health and disease 20080919

<h4>Background</h4>The APOA1-C3-A5 gene cluster plays an important role in the regulation of lipids. Asian Indians have an increased tendency for abnormal lipid levels and high risk of Coronary Artery Disease (CAD). Therefore, the present study aimed to elucidate the relationship of four single nucleotide polymorphisms (SNPs) in the Apo11q cluster, namely the -75G>A, +83C>T SNPs in the APOA1 gene, the Sac1 SNP in the APOC3 gene and the S19W variant in the APOA5 gene to plasma lipids and CAD in 1 ...[more]

PMID: 18801202

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Project description:BACKGROUND: Central obesity is a rising epidemic, and often occurs in parallel with dyslipidemia. Furthermore, enhancement of ectopic fat deposition has been observed in both human studies and animal models of altered lipidemic control. Though APOA1/C3/A4/A5 genetic polymorphisms are associated with dyslipidemia, their effect on central obesity is less known. METHOD: The anthropometric and metabolic parameters were taken from obese (body mass index (BMI) ?25?kg?m(-2)) and non-obese healthy (BMI <25) Taiwanese patients at the initiation weight-loss intervention and 6 months later. The effects of APOA1/C3/A4/A5 genetic polymorphisms were analyzed cross-sectionally and longitudinally. Gender contributions were specifically examined. PATIENTS: Three hundred and ninety-eight participants (obese n=262; non-obese healthy n=136) were recruited in total, and 130 obese patients underwent weight-loss treatments. RESULTS: APOA5 rs662799 minor allele carriage was associated with unfavorable metabolic profiles in obese but not non-obese individuals at baseline. Further analysis identified gender-genotype interactions in waist-hip ratio (WHR), and that one rs662799 minor allele increased 0.032 WHR unit in obese males as analyzed by linear regression adjusted for age, BMI and plasma triglyceride (TG) (95% confidence interval (CI)=0.014-0.050, P=0.001). The rs662799-associated WHR elevation resulted in increased frequency of central obesity (WHR ?1.0) in rs662799 carrying obese males as analyzed by binary logistic regression adjusted for age, BMI and plasma TG (odds ratio=6.52, 95% CI=1.87-22.73, P=0.003). In contrast, APOA5 rs662799 and central obesity were no longer correlated 6 months into weight-loss treatments, owing to significant WHR reductions in male rs662799 minor allele carriers (P=0.001). Meanwhile, hypertriglyceridemia was more prevalent in both male and female obese rs662799 minor allele carriers at baseline (males, P=0.034, females, P=0.007). CONCLUSION: This study highlights the gender-specific and weight-sensitive effects of APOA5 rs662799 on central obesity in Taiwanese individuals, and that these effects are dyslipidemia-independent and weight-loss responsive.

Project description:BackgroundDyslipidemia contributes to the risk of many diseases, including stroke, cardiovascular disease and metabolic-related diseases. Previous studies have indicated that single nucleotide polymorphisms (SNPs) are associated with different levels of serum lipid. Therefore, this study explored the relationship between the APOA1/C3/A4/A5-ZPR1-BUD13 gene cluster gene polymorphisms and dyslipidemia in the total sample population and stratified by genders in a northeast Chinese population.MethodsA total of 3,850 participants from Jilin Province, China, were enrolled in our study, and their serum lipid levels were measured. Six functional SNPs (APOA1 rs5072, APOC3 rs5128, APOA4 rs5104, APOA5 rs651821, ZPR1 rs2075294 and BUD13 rs10488698) were genotyped using polymerase chain reaction and MALDI-TOF-MS. Logistic regression analysis was performed to explore the relationship of APOA1/C3/A4/A5-ZPR1-BUD13 gene cluster gene polymorphisms with dyslipidemia. Linkage disequilibrium and haplotype analyses were performed with the SNPStats program and Haploview software.ResultsAll SNPs conformed to Hardy-Weinberg equilibrium. Logistic regression analysis revealed that rs5072, rs5128 and rs651821 were associated with hypertriglyceridemia, rs5104 and rs651821 were associated with low-HDL cholesterolemia in overall group. rs651821 was associated with hypertriglyceridemia and low-HDL cholesterolemia in both the male and female group. However, among females, rs5072 was observed to be associated with hypertriglyceridemia. Haplotype analysis showed that haplotypes TGCCGC and CAGCGC were associated with dyslipidemia in the overall, male and female groups.ConclusionSNPs in the APOA1/C3/A4/A5-ZPR1-BUD13 gene cluster were associated with dyslipidemia. Furthermore, the association of APOA1 rs5072 in this gene cluster with dyslipidemia differed between genders; thus, additional studies are needed to confirm this conclusion, and the mechanisms underlying these results warrant further exploration.

Dataset Information

Genetic studies on the APOA1-C3-A5 gene cluster in Asian Indians with premature coronary artery disease.

Publications

Genetic studies on the APOA1-C3-A5 gene cluster in Asian Indians with premature coronary artery disease.

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