Association of the Functional Variant in the 3-Hydroxy-3-Methylglutaryl-Coenzyme A Reductase Gene With Low-Density Lipoprotein-Cholesterol in Japanese

作者：Hiura Yumiko; Tabara Yasuharu; Kokubo Yoshihiro; Okamura Tomonori; Goto Yoichi; Nonogi Hiroshi; Miki Tetsuro; Tomoike Hitonobu; Iwai Naoharu^*

来源：Circulation Journal, 2010, 74(3): 518-522.

DOI：10.1253/circj.CJ-09-0790

• Genetics
• Lipids
• Myocardial infarction
• Polymorphism

Background. The association between single nucleotide polymorphisms (SNPs) at 3-hydroxy-3-methylglutarylcoenzyme 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=4.91 x10(-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. (Circ J 2010; 74: 518-522)

• 出版日期2010-3