title: Association of genetic variants with coronary artery disease and ischemic stroke in a longitudinal population-based genetic epidemiological study.
abstract: Our previous studies identified nine genes and chromosomal region 3q28 as susceptibility loci for myocardial infarction, ischemic stroke or chronic kidney disease by genome-wide or candidate gene association studies. As coronary artery disease (CAD) and ischemic stroke may share genetic architecture, certain genetic variants may confer susceptibility to the two diseases. The present study examined the association of 13 polymorphisms at these 10 loci with the prevalence of CAD or ischemic stroke in community-dwelling individuals, with the aim of identifying genetic variants that confer susceptibility to the two conditions. Study subjects (170 with CAD, 117 with ischemic stroke and 5,718 controls) were recruited to the Inabe Health and Longevity Study, a longitudinal genetic epidemiological study of atherosclerotic, cardiovascular and metabolic diseases. The subjects were recruited from individuals who visited for an annual health checkup and they were followed up each year (mean follow-up period, 5 years). Longitudinal analysis with a generalized estimating equation, and with adjustment for age, gender, body mass index, smoking status, the prevalence of hypertension, diabetes mellitus and dyslipidemia and the serum concentration of creatinine, revealed that rs2074380 (G→A) and rs2074381 (A→G) of the α-kinase 1 (ALPK1) gene and rs8089 (T→G) of the thrombospondin 2 (THBS2) gene were significantly (P<2×10-16) associated with the prevalence of CAD, with theAAgenotype of rs2074380 andGGgenotypes of rs2074381 and rs8089 being protective against this condition. Similar analysis revealed that rs9846911 (A→G) at chromosome 3q28, rs2074381 ofALPK1, rs8089 ofTHBS2and rs6046 (G→A) of the coagulation factor VII gene were significantly (P<2×10-16) associated with the prevalence of ischemic stroke, with theGGgenotypes of rs9846911, rs2074381 and rs8089 and theAAgenotype of rs6046 being protective against this condition.ALPK1andTHBS2may thus be susceptibility loci for CAD and ischemic stroke.
authors.affiliation: Department of Human Functional Genomics, Life Science Research Center, Mie University, Tsu, Mie 514-8507, Japan ; Core Research for Evolutional Science and Technology, Japan Science and Technology Agency, Chiyoda-ku, Tokyo 102-0075, Japan.
authors.forename: Yoshiji
authors.initials: Y
authors.lastname: Yamada
authors.affiliation: Core Research for Evolutional Science and Technology, Japan Science and Technology Agency, Chiyoda-ku, Tokyo 102-0075, Japan ; Department of Scientific and Engineering Simulation, Graduate School of Engineering, Nagoya Institute of Technology, Nagoya, Aichi 466-8555, Japan.
authors.forename: Kota
authors.initials: K
authors.lastname: Matsui
authors.affiliation: Core Research for Evolutional Science and Technology, Japan Science and Technology Agency, Chiyoda-ku, Tokyo 102-0075, Japan ; Department of Scientific and Engineering Simulation, Graduate School of Engineering, Nagoya Institute of Technology, Nagoya, Aichi 466-8555, Japan.
authors.forename: Ichiro
authors.initials: I
authors.lastname: Takeuchi
authors.affiliation: Department of Cardiovascular Medicine, Inabe General Hospital, Inabe, Mie 511-0428, Japan.
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Fujimaki
keywords: coronary artery disease; genetics; ischemic stroke; longitudinal study; polymorphism