Association of the functional variant in the 3-hydroxy-3-methylglutaryl-coenzyme a reductase gene with low-density lipoprotein-cholesterol in Japanese

Circ J. 2010 Mar;74(3):518-22. doi: 10.1253/circj.cj-09-0790. Epub 2010 Feb 9.

Abstract

Background: The association between single nucleotide polymorphisms (SNPs) at 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) and low-density lipoprotein-cholesterol (LDL-C) levels has been well replicated in genome-wide association studies (GWAS) of white populations. Recently, the common intronic SNP of HMGCR (rs3846662) has been reported to be a functional variant, influencing the alternative splicing of exon 13. The aim of this study was to examine the association between rs3846662 of HMGCR and the level of LDL-C in Japanese.

Methods and results: Significant differences in LDL-C levels were observed among the genotypes of rs3846662 (P=0.0002 (n=2,686) and P=0.004 (n=2,110)) for the Suita and Ehime samples, respectively. The G allele of rs3846662 was associated with higher LDL-C levels (beta, 3.56; P=4.91x10(-5)). Consistent with this observation, the risk G allele at rs3846662 was more prevalent in subjects with myocardial infarction (MI) (n=701) than in subjects without MI (n=3,118); 0.559 and 0.511 in MI cases and controls, respectively (nominal P=0.0038). The odds ratio adjusted for age, sex, diabetes, hypertension, and drinking and smoking habits was 1.15 (95% confidence interval 1.04-1.28; P=0.0075).

Conclusions: The previously reported association of rs3846662 with LDL-C levels was replicated in the present Suita and Ehime samples. The LDL-associated SNP, rs3846662, appears to confer susceptibility to MI in Japanese.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Alcohol Drinking / epidemiology
  • Alternative Splicing / genetics
  • Asian People / genetics*
  • Asian People / statistics & numerical data*
  • Cholesterol, LDL / blood*
  • Diabetes Mellitus / epidemiology
  • Female
  • Genetic Predisposition to Disease / epidemiology
  • Genetic Variation
  • Genotype
  • Humans
  • Hydroxymethylglutaryl CoA Reductases / genetics*
  • Hydroxymethylglutaryl CoA Reductases / metabolism
  • Hypertension / epidemiology
  • Introns / genetics
  • Japan / epidemiology
  • Male
  • Middle Aged
  • Myocardial Infarction / epidemiology*
  • Myocardial Infarction / genetics*
  • Polymorphism, Single Nucleotide
  • Prevalence
  • Risk Factors
  • Smoking / epidemiology

Substances

  • Cholesterol, LDL
  • Hydroxymethylglutaryl CoA Reductases