Association of a genetic variant in the apolipoprotein A5 gene with the metabolic syndrome in Chinese

Abstract

INTRODUCTION: We previously reported that the single nucleotide polymorphism (SNP) rs662799 (-1131T>C) in the apolipoprotein A5 gene (APOA5) was an important determinant of plasma triglycerides in both Hong Kong and Guangzhou Chinese. We, therefore, investigated the association of SNPs in APOA5 with the metabolic syndrome (MetS) in the Hong Kong and Guangzhou Chinese. METHODS: MetS was defined according to the consensus criteria proposed jointly by several organizations in 2009. Five tagging SNPs were genotyped in 1330 unrelated subjects from the Hong Kong Cardiovascular Risk Factor Prevalence Study cohort with follow-up after a median interval of 6.4 years. 1952 subjects from the Guangzhou Biobank Cohort Study-Cardiovascular Disease Subcohort were used to replicate the findings. RESULTS: The minor allele of rs662799 was significantly associated with higher odds for the MetS in Hong Kong subjects at both baseline (OR=1.47, P=0.00082) and follow-up (OR=1.30, P=0.010). A similar association was found in Guangzhou subjects (OR=1.27, P=0.0041). In a pooled sample of Hong Kong subjects at follow-up and Guangzhou subjects, this SNP was also associated with HDL and LDL cholesterol (P<0.001 and 0.010 respectively). All these associations disappeared after further adjusting for plasma triglycerides (P>0.05). In a meta-analysis of 6 studies, the combined OR (95% CI) was 1.38 (1.25-1.52) for the TC + CC genotype compared to the TT genotype (P<0.00001). CONCLUSION: The association of -1131T>C polymorphism in APOA5 with the MetS was mainly due to its strong effect on plasma triglycerides. Further studies are needed to assess the utility of this genetic marker in risk stratification.