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

Yumiko Hiura, Yasuharu Tabara, Yoshihiro Kokubo, Tomonori Okamura, Yoichi Goto, Hiroshi Nonogi, Tetsuro Miki, Hitonobu Tomoike, Naoharu Iwai

Research output: Contribution to journalArticle

12 Citations (Scopus)

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 languageEnglish
Pages (from-to)518-522
Number of pages5
JournalCirculation Journal
Volume74
Issue number3
DOIs
Publication statusPublished - 2010 Mar
Externally publishedYes

Fingerprint

LDL Cholesterol
Oxidoreductases
Myocardial Infarction
Single Nucleotide Polymorphism
Genes
Alleles
Genome-Wide Association Study
Alternative Splicing
HDL Cholesterol
Drinking
Habits
Exons
Smoking
Odds Ratio
Genotype
3-hydroxy-3-methylglutaryl-coenzyme A
Confidence Intervals
Hypertension
Population

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 journalArticle

Hiura, Yumiko ; Tabara, Yasuharu ; Kokubo, Yoshihiro ; Okamura, Tomonori ; Goto, Yoichi ; Nonogi, Hiroshi ; Miki, Tetsuro ; Tomoike, Hitonobu ; Iwai, Naoharu. / Association of the functional variant in the 3-hydroxy-3-methylglutaryl- coenzyme A reductase gene with low-density lipoprotein-cholesterol in Japanese. In: Circulation Journal. 2010 ; Vol. 74, No. 3. pp. 518-522.
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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.",
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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.

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