title: Association of a genetic variant of the ZPR1 zinc finger gene with type 2 diabetes mellitus.
abstract: Various loci and genes that confer susceptibility to coronary heart disease (CHD) have been identified in Caucasian populations by genome-wide association studies (GWASs). As type 2 diabetes mellitus (DM) is an important risk factor for CHD, we hypothesized that certain polymorphisms may contribute to the genetic susceptibility to CHD through affecting the susceptibility to type 2 DM. The purpose of the present study was to examine a possible association of type 2 DM in Japanese individuals with 29 polymorphisms identified as susceptibility loci for CHD by meta-analyses of the GWASs. The study subjects comprised of 3,757 individuals (1,444 subjects with type 2 DM and 2,313 controls). The polymorphism genotypes were determined by the multiplex bead-based Luminex assay, which combines the polymerase chain reaction and sequence-specific oligonucleotide probes with suspension array technology. To compensate for multiple comparisons of genotypes, the criterion of a false discovery rate (FDR) ≤0.05 was adopted for testing the statistical significance of the association. The comparisons of allele frequencies by the χ2test revealed that the rs964184 (C→G) of the ZPR1 zinc finger gene (ZPR1) was significantly associated (P=0.0017; FDR=0.050) with type 2 DM. Multivariable logistic regression analysis with adjustment for age, gender and body mass index revealed that rs964184 ofZPR1was significantly associated (P=0.0012; odds ratio, 1.25; dominant model) with type 2 DM with the minorGallele representing a risk factor for this condition. Fasting plasma glucose levels (P=0.0076) and blood glycosylated hemoglobin contents (P=0.0132) significantly differed amongZPR1genotypes with theGallele associated with increases in these parameters.ZPR1may thus be a susceptibility locus for type 2 DM in Japanese individuals.
authors.affiliation: Department of Cardiology, Gifu Prefectural General Medical Center, Gifu 500-8717, Japan.
authors.forename: Fumitaka
authors.initials: F
authors.lastname: Tokoro
authors.affiliation: Department of Cardiology, Gifu Prefectural General Medical Center, Gifu 500-8717, Japan.
authors.forename: Reiko
authors.initials: R
authors.lastname: Matsuoka
authors.affiliation: Department of Cardiology, Gifu Prefectural General Medical Center, Gifu 500-8717, Japan.
authors.forename: Shintaro
authors.initials: S
authors.lastname: Abe
authors.affiliation: Department of Cardiology, Gifu Prefectural General Medical Center, Gifu 500-8717, Japan.
authors.forename: Masazumi
authors.initials: M
authors.lastname: Arai
authors.affiliation: Department of Cardiology, Gifu Prefectural General Medical Center, Gifu 500-8717, Japan.
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Noda
authors.affiliation: Department of Cardiology, Gifu Prefectural General Medical Center, Gifu 500-8717, Japan.
authors.forename: Sachiro
authors.initials: S
authors.lastname: Watanabe
authors.affiliation: Department of Cardiovascular Medicine, Gifu Prefectural Tajimi Hospital, Tajimi, Gifu 507-8522, Japan.
authors.forename: Hideki
authors.initials: H
authors.lastname: Horibe
authors.affiliation: Department of Cardiovascular Medicine, Inabe General Hospital, Inabe, Mie 511-0428, Japan.
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Fujimaki
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 Internal Medicine, Meitoh Hospital, Nagoya, Aichi 465-0025, Japan.
authors.forename: Kimihiko
authors.initials: K
authors.lastname: Kato
authors.affiliation: Department of Cardiology, Gifu University Graduate School of Medicine, Gifu 501-1194, Japan.
authors.forename: Shinya
authors.initials: S
authors.lastname: Minatoguchi
authors.affiliation: Department of Human Functional Genomics, Life Science Research Center, Mie University, Tsu, Mie 514-8507, Japan.
authors.forename: Yoshiji
authors.initials: Y
authors.lastname: Yamada
keywords: ZPR1 zinc finger gene; diabetes mellitus; genetics; polymorphism