Abstract
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 (ß, 3.56; P=4.91×10-5). 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.
| Original language | English |
|---|---|
| Pages (from-to) | 518-522 |
| Number of pages | 5 |
| Journal | Circulation Journal |
| Volume | 74 |
| Issue number | 3 |
| DOIs | |
| Publication status | Published - 2010 Mar |
| Externally published | Yes |
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Keywords
- Genetics
- Lipids
- Myocardial infarction
- Polymorphism
ASJC Scopus subject areas
- Cardiology and Cardiovascular Medicine
Cite this
Association of the functional variant in the 3-hydroxy-3-methylglutaryl- coenzyme A reductase gene with low-density lipoprotein-cholesterol in Japanese. / Hiura, Yumiko; Tabara, Yasuharu; Kokubo, Yoshihiro; Okamura, Tomonori; Goto, Yoichi; Nonogi, Hiroshi; Miki, Tetsuro; Tomoike, Hitonobu; Iwai, Naoharu.
In: Circulation Journal, Vol. 74, No. 3, 03.2010, p. 518-522.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Association of the functional variant in the 3-hydroxy-3-methylglutaryl- coenzyme A reductase gene with low-density lipoprotein-cholesterol in Japanese
AU - Hiura, Yumiko
AU - Tabara, Yasuharu
AU - Kokubo, Yoshihiro
AU - Okamura, Tomonori
AU - Goto, Yoichi
AU - Nonogi, Hiroshi
AU - Miki, Tetsuro
AU - Tomoike, Hitonobu
AU - Iwai, Naoharu
PY - 2010/3
Y1 - 2010/3
N2 - 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 (ß, 3.56; P=4.91×10-5). 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.
AB - 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 (ß, 3.56; P=4.91×10-5). 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.
KW - Genetics
KW - Lipids
KW - Myocardial infarction
KW - Polymorphism
UR - http://www.scopus.com/inward/record.url?scp=77649197488&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=77649197488&partnerID=8YFLogxK
U2 - 10.1253/circj.CJ-09-0790
DO - 10.1253/circj.CJ-09-0790
M3 - Article
C2 - 20145341
AN - SCOPUS:77649197488
VL - 74
SP - 518
EP - 522
JO - Circulation Journal
JF - Circulation Journal
SN - 1346-9843
IS - 3
ER -