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


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.
Department of Epidemiology, Research Institute, National Cardiovascular Center, Suita, Japan.
Yumiko
Y
Hiura
Yasuharu
Y
Tabara
Yoshihiro
Y
Kokubo
Tomonori
T
Okamura
Yoichi
Y
Goto
Hiroshi
H
Nonogi
Tetsuro
T
Miki
Hitonobu
H
Tomoike
Naoharu
N
Iwai
D000328:Adult; D000368:Aged; D000428:Alcohol Drinking / Q000453:epidemiology; D017398:Alternative Splicing / Q000235:genetics; D044466:Asian People / Q000235:genetics* / Q000706:statistics & numerical data*; D008078:Cholesterol, LDL / Q000097:blood*; D003920:Diabetes Mellitus / Q000453:epidemiology; D005260:Female; D020022:Genetic Predisposition to Disease / Q000453:epidemiology; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D006903:Hydroxymethylglutaryl CoA Reductases / Q000235:genetics* / Q000378:metabolism; D006973:Hypertension / Q000453:epidemiology; D007438:Introns / Q000235:genetics; D007564:Japan / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000453:epidemiology* / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D015995:Prevalence; D012307:Risk Factors; D012907:Smoking / Q000453:epidemiology
D008078:Cholesterol, LDL; D006903:Hydroxymethylglutaryl CoA Reductases