title: Association between polymorphisms of the α-kinase 1 gene and type 2 diabetes mellitus in community-dwelling individuals.
abstract: We previously demonstrated that the α-kinase 1 gene (ALPK1) is a susceptibility locus for chronic kidney disease in individuals with diabetes mellitus (DM) by a genome-wide association study. Although genetic variants ofALPK1have been associated with chronic kidney disease in individuals with DM, whetherALPK1is a susceptibility locus for DM has not been elucidated. The purpose of the present study was to investigate a possible association of the rs2074388 (A→G, Asp565Gly) or rs2074379 (A→G, Ile732Met) variants ofALPK1with type 2 DM in community-dwelling individuals. The study subjects comprised 5,959 community-dwelling individuals (495 subjects with type 2 DM and 5,464 controls) who were recruited to a population-based cohort study in Inabe, Mie, Japan. The comparisons of allele frequencies or genotype distributions using the Chi-square test revealed that the rs2074388 and rs2074379 variants ofALPK1were significantly associated with type 2 DM (P<0.05). A multivariable logistic regression analysis with adjustment for age, gender, body mass index and smoking status revealed that the rs2074388 (P=0.0051; odds ratio, 1.32) and rs2074379 (P=0.0058; odds ratio, 1.32) variants were significantly associated with type 2 DM. The haplotype analysis of these polymorphisms revealed that the frequency of the major haplotype, A (rs2074388)-A (rs2074379), was significantly lower, whereas that of the minor haplotype G-G was significantly higher in subjects with type 2 DM compared to controls. Thus,ALPK1may be a susceptible gene for type 2 DM in community-dwelling Japanese individuals.
authors.affiliation: Department of Cardiology, Japanese Red Cross Nagoya First Hospital, Nagoya, Aichi, Japan.
authors.forename: Shigetaka
authors.initials: S
authors.lastname: Shimokata
authors.affiliation: Department of Cardiology, Japanese Red Cross Nagoya First Hospital, Nagoya, Aichi, Japan.
authors.forename: Mitsutoshi
authors.initials: M
authors.lastname: Oguri
authors.affiliation: Department of Cardiovascular Medicine, Inabe General Hospital, Inabe, Mie, Japan.
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Fujimaki
authors.affiliation: Department of Cardiovascular Medicine, Gifu Prefectural Tajimi Hospital, Tajimi, Gifu, Japan.
authors.forename: Hideki
authors.initials: H
authors.lastname: Horibe
authors.affiliation: Meitoh Hospital, Nagoya, Aichi, Japan ; Department of Human Functional Genomics, Life Science Research Center, Mie University, Tsu, Mie, Japan.
authors.forename: Kimihiko
authors.initials: K
authors.lastname: Kato
authors.affiliation: Department of Human Functional Genomics, Life Science Research Center, Mie University, Tsu, Mie, Japan.
authors.forename: Yoshiji
authors.initials: Y
authors.lastname: Yamada
keywords: cohort study; genetics; polymorphism; type 2 diabetes mellitus