title: Association of genetic variants of the α-kinase 1 gene with type 2 diabetes mellitus in a longitudinal population-based genetic epidemiological study.
abstract: Previously, our studies identified nine genes and the chromosomal region 3q28 as susceptibility loci for myocardial infarction, ischemic stroke or chronic kidney disease in individuals by genome-wide or candidate gene association studies. The present study examined the possible association of 13 polymorphisms at these 10 loci with the prevalence of type 2 diabetes mellitus (DM) in community-dwelling individuals. Study subjects comprised 6,027 individuals (797 subjects with type 2 DM and 5,230 controls) who 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, 5 years). Longitudinal analysis with a generalized estimating equation and with adjustment for age, gender and body mass index (BMI) revealed that rs2116519 (C→T) ofFAM78B(P=0.0188), as well as rs2074379 (G→A, P=0.0121) and rs2074388 (A→G, P=0.0053) ofALPK1were significantly (P<0.05) associated with the prevalence of type 2 DM. Longitudinal analysis with a generalized linear mixed-effect model and with adjustment for age, gender and BMI among all the individuals revealed that rs2116519, rs2074379 and rs2074388 were significantly associated with fasting plasma glucose level (P=0.0352, 0.0017 and 0.0010, respectively) and to blood glycosylated hemoglobin (hemoglobin A1c) content (P=0.0065, 0.0090 and 0.0079, respectively). Similar analysis among individuals not taking antidiabetic medication revealed that rs2074379 and rs2074388 were associated with the fasting plasma glucose level (P=0.0073 and 0.0042, respectively) and blood hemoglobin A1ccontent (P=0.0142 and 0.0126, respectively), whereas rs2116519 was associated with blood hemoglobin A1ccontent only (P=0.0470).ALPK1may thus be a susceptibility gene for type 2 DM.
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, Tokyo 102-0076, Japan.
authors.forename: Yoshiji
authors.initials: Y
authors.lastname: Yamada
authors.affiliation: Core Research for Evolutional Science and Technology, Japan Science and Technology Agency, Tokyo 102-0076, 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, Tokyo 102-0076, 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 Cardiology, Japanese Red Cross Nagoya First Hospital, Nagoya, Aichi 453-8511, Japan.
authors.forename: Mitsutoshi
authors.initials: M
authors.lastname: Oguri
authors.affiliation: Department of Cardiovascular Medicine, Inabe General Hospital, Inabe, Mie 511-0428, Japan.
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Fujimaki
keywords: genetic epidemiology; genetics; longitudinal study; polymorphism; type 2 diabetes mellitus