Heterogeneous Effects of Association Between Blood Pressure Loci and Coronary Artery Disease in East Asian Individuals

• Takeuchi Fumihiko

  Department of Gene Diagnostics and Therapeutics, Research Institute, National Center for Global Health and Medicine

• Isono Masato

  Department of Gene Diagnostics and Therapeutics, Research Institute, National Center for Global Health and Medicine

• Yamamoto Ken

  Department of Molecular Genetics, Medical Institute of Bioregulation, Kyushu University

• Yokota Mitsuhiro

  Department of Genome Science, Aichi-Gakuin University, School of Dentistry

• Akiyama Koichi

  Department of Gene Diagnostics and Therapeutics, Research Institute, National Center for Global Health and Medicine

• Katsuya Tomohiro

  Department of Clinical Gene Therapy, Osaka University Graduate School of Medicine Department of Geriatric Medicine and Nephrology, Osaka University Graduate School of Medicine

• Kim Hyo-Soo

  Department of Internal Medicine, Cardiovascular Center, Seoul National University Hospital

• Park Jeong Euy

  Division of Cardiology, Samsung Medical Center

• Jang Yangsoo

  Cardiology Division, Department of Internal Medicine, Cardiovascular Genome Center, Yonsei University College of Medicine,

• Lee Ji-Young

  Center for Genome Science, Korea National Institute of Health, KCDC

• AGEN Consortium

• Lee Jong-Young

  Center for Genome Science, Korea National Institute of Health, KCDC

• Kato Norihiro

  Department of Gene Diagnostics and Therapeutics, Research Institute, National Center for Global Health and Medicine

Abstract

Background:A coronary artery disease (CAD) association study of genetic loci previously identified as being associated with blood pressure (BP) was performed in east Asian populations.Methods and Results:Nine single nucleotide polymorphisms (SNPs) from 9 candidate loci robustly confirmed to be associated with BP in east Asian people, were genotyped. Genotyping was done in up to 17,785 CAD case-control samples (6,522 cases and 11,263 controls). We then tested the associations with other metabolic traits (n≤17,900) and with type 2 diabetes (931 cases and 1,404 controls), and looked up the datasets in silico in other populations. Significant (adjusted P<0.05) CAD associations were found for 5 BP loci: 3 new CAD associations atFIGN,FGF5andNPR3, and 2 previously reported ones atATP2B1andCNNM2. The strongest CAD association was detected atATP2B1rs2681472 (P=1.7×10^–8), in the direction inverted to what is generally recognized for BP in the epidemiological studies.CNNM2rs12413409 showed significant association with CAD (P=8.7×10^–7) and BMI (P=3.5×10^–8, when meta-analyzed with 75,807 east Asian people). The genetic risk score combining BP-raising alleles at each of the SNPs was positively associated with CAD (P=0.011).Conclusions:A substantial proportion of genetic variants associated with BP were also associated with the risk of CAD in east Asian people, and there was some counter-evidence for causal inference. (Circ J 2015; 79: 830–838)

Journal

• Circulation Journal

  Circulation Journal 79 (4), 830-838, 2015

  The Japanese Circulation Society

Keywords

• Blood pressure
• Coronary artery disease
• Genetic susceptibility

Details

• CRID: 1390001205107468800
• NII Article ID: 40020412372
• NII Article ID: 130005130251
• NII Book ID: AA11591968
• DOI: 10.1253/circj.cj-14-0841
• ISSN: 13474820
• ISSN: 13469843
• NDL BIB ID: 026283908
• PubMed: 25740055
• Web Site: https://ndlsearch.ndl.go.jp/books/R000000004-I026283908
• Web Site: https://www.jstage.jst.go.jp/article/circj/79/4/79_CJ-14-0841/_pdf
• Web Site: https://search.jamas.or.jp/link/ui/2015311441
• Text Lang: en
• Data Source:
  • JaLC
  • NDL
  • Crossref
  • PubMed
  • CiNii Articles
  • KAKEN
• Abstract License Flag: Disallowed