Abstract

The apolipoprotein A5 (APOA5) gene −1131T>C (rs662799) has been suggested to be involved in the pathway of lipid homeostasis and the development of metabolic syndrome (MetS). However, the findings are not consistent. To systematically evaluate the associations between −1131T>C polymorphism and fasting lipid parameters and the risk of MetS, we conducted a case-control study in a Chinese population and a meta-analysis. The findings from 1840 Chinese participants indicated that the C allele carriers had significantly higher fasting total cholesterol (TC), triglycerides (TG) and lower HDL-cholesterol (HDL-C) than the TT homozygotes carriers. The −1131C allele was also found to be significantly associated with increased risk of MetS (OR = 1.40, 95% confidence interval (CI) = 1.15, 1.69) compared to the TT homozygotes. In the meta-analysis of 51,868 participants from 46 East Asian studies, 26 European studies and 19 studies of other ethnic groups, the −1131C allele was associated with higher fasting TC (weighted mean difference (WMD) = 0.08 mmol/L, 95% CI = 0.05, 0.10, P = 1.74×10−9), TG (WMD = 0.30 mmol/L, 95% CI = 0.26, 0.33, P = 1.87×10−55), LDL-cholesterol (LDL-C) (WMD = 0.04 mmol/L, 95% CI = 0.02, 0.07, P = 0.002), and lower HDL-C (WMD = −0.05 mmol/L, 95% CI = −0.06,−0.04, P = 1.88×10−21), respectively. Based on 12 studies with 5,573 MetS cases and 8,290 controls from 5 East Asian studies, 5 European studies and 2 studies of other ethnic groups, the −1131C allele was associated with increased risk of MetS with an OR (95% CI) = 1.33 (1.16, 1.53) in the overall population, 1.43 (1.29, 1.58) in East Asian and 1.30 (0.94, 1.78) in European populations. In conclusion, the −1131C allele may be associated with elevated levels of fasting TG, TC, LDL-C and decreased HDL-C, and increased risk of MetS, especially in East Asians.

Highlights

  • Metabolic syndrome (MetS), characterized by visceral obesity, dyslipidemia, hypertension and hyperglycemia, has become one of the major public health challenges worldwide [1]

  • The +1891T.C in apolipoprotein A5 (APOA5) gene was reported associated with MetS in a European genome-wide association studies (GWAS) [3]

  • Under the dominant model and adjusted for age and gender, the carriers with the 21131C allele were found to have an increased risk for MetS (OR = 1.40, 95% confidence interval (CI) = 1.15, 1.69)

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Summary

Introduction

Metabolic syndrome (MetS), characterized by visceral obesity, dyslipidemia, hypertension and hyperglycemia, has become one of the major public health challenges worldwide [1]. The prevalence of MetS is currently around 30% and is rising worldwide [2]. Recent candidate gene and genome-wide association studies (GWAS) have identified a few susceptibility loci for MetS [3,4]. The apolipoprotein A5 (APOA5) gene has been found to be associated with the increased risk of MetS. The +1891T.C (rs2266788) in APOA5 gene was reported associated with MetS in a European GWAS [3]. Another intergenic locus in APOA1/C3/A4/A5 gene cluster region, rs964184, was identified associated with MetS in Finnish populations by a GWAS [4]. APOA5 is considered a potential biomarker for MetS

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