Identification of Genetic Markers Associated With High-Density Lipoprotein-Cholesterol by Genome-Wide Screening in a Japanese Population The Suita Study

Yumiko Hiura; Chun-Shen Shen; Yoshihiro Kokubo; Tomonori Okamura; Takayuki Morisaki; Hitonobu Tomoike; Teruhiko Yoshida; Hiromi Sakamoto; Yoichi Goto; Hiroshi Nonogi; Naoharu Iwai

doi:10.1253/circj.CJ-08-1101

Molecular Cardiology

Identification of Genetic Markers Associated With High-Density Lipoprotein-Cholesterol by Genome-Wide Screening in a Japanese Population

The Suita Study

Yumiko Hiura, Chun-Shen Shen, Yoshihiro Kokubo, Tomonori Okamura, Takayuki Morisaki, Hitonobu Tomoike, Teruhiko Yoshida, Hiromi Sakamoto, Yoichi Goto, Hiroshi Nonogi, Naoharu Iwai

Author information

Yumiko Hiura
Department of Epidemiology, Research Institute, National Cardiovascular Center
Chun-Shen Shen
Department of Epidemiology, Research Institute, National Cardiovascular Center
Yoshihiro Kokubo
Division of Preventive Cardiology, National Cardiovascular Center
Tomonori Okamura
Division of Preventive Cardiology, National Cardiovascular Center
Takayuki Morisaki
Department of Biosciences, Research Institute, National Cardiovascular Center
Hitonobu Tomoike
Division of Preventive Cardiology, National Cardiovascular Center
Teruhiko Yoshida
Genetics Division, National Cancer Center Research Institute
Hiromi Sakamoto
Genetics Division, National Cancer Center Research Institute
Yoichi Goto
Division of Cardiology, National Cardiovascular Center
Hiroshi Nonogi
Division of Cardiology, National Cardiovascular Center
Naoharu Iwai
Department of Epidemiology, Research Institute, National Cardiovascular Center
Division of Cardiology, National Cardiovascular Center

Keywords: Genetics, HDL-cholesterol, Single nucleotide polymorphism

JOURNAL FREE ACCESS

2009 Volume 73 Issue 6 Pages 1119-1126

DOI https://doi.org/10.1253/circj.CJ-08-1101

View "Advance Publication" version (April 10, 2009).

Details

Abstract

Background: Recent genome-wide association studies (GWAS) have identified genes or loci affecting lipid levels. Given the difference in allele frequencies and linkage disequilibrium patterns across the populations, a GWAS was conducted using the Illumina 550K in a Japanese population (n=900) in search of population-specific genetic variations associated with high-density lipoprotein (HDL)-cholesterol. Methods and Results: Among the 368,274 single nucleotide polymorphisms (SNPs) with a minor allele frequency of at least 0.1, 43 SNPs exceeded the arbitrary threshold of -log₁₀P >4.0. The most significant SNP was rs3764261, located 5'upstream of CETP, exhibiting a -log₁₀P value of 6.17. Increasing the sample size by genotyping in the additional Suita sample (n=1,810) further improved the level of significance, with each additional copy of the minor allele being associated with an increase in HDL-cholesterol by 6.2 mg/dl (P =3.4×10^-12). Interestingly, the minor allele was more prevalent in cases with myocardial infarction than in controls (0.221 vs 0.196, nominal P=0.02). Conclusions: The association between genetic variants at CETP and HDL-cholesterol was replicated in our sample. None of the genetic variants exerted a greater influence on HDL levels than those at CETP. Associations for the top-ranked SNPs need to be tested for further replication in an independent sample. (Circ J 2009; 73: 1119-1126)

Corresponding author

Register with J-STAGE for free!