Association of a genetic variant of the ZPR1 zinc finger gene with type 2 diabetes mellitus

Tokoro,Fumitaka; Matsuoka,Reiko; Abe,Shintaro; Arai,Masazumi; Noda,Toshiyuki; Watanabe,Sachiro; Horibe,Hideki; Fujimaki,Tetsuo; Oguri,Mitsutoshi; Kato,Kimihiko; Minatoguchi,Shinya; Yamada,Yoshiji

doi:10.3892/br.2014.379

Association of a genetic variant of the ZPR1 zinc finger gene with type 2 diabetes mellitus

Authors:
- Fumitaka Tokoro
- Reiko Matsuoka
- Shintaro Abe
- Masazumi Arai
- Toshiyuki Noda
- Sachiro Watanabe
- Hideki Horibe
- Tetsuo Fujimaki
- Mitsutoshi Oguri
- Kimihiko Kato
- Shinya Minatoguchi
- Yoshiji Yamada
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Affiliations: Department of Cardiology, Gifu Prefectural General Medical Center, Gifu 500‑8717, Japan, Department of Cardiovascular Medicine, Gifu Prefectural Tajimi Hospital, Tajimi, Gifu 507‑8522, Japan, Department of Cardiovascular Medicine, Inabe General Hospital, Inabe, Mie 511‑0428, Japan, Department of Cardiology, Japanese Red Cross Nagoya First Hospital, Nagoya, Aichi 453‑8511, Japan, Department of Internal Medicine, Meitoh Hospital, Nagoya, Aichi 465-0025, Japan, Department of Cardiology, Gifu University Graduate School of Medicine, Gifu 501‑1194, Japan, Department of Human Functional Genomics, Life Science Research Center, Mie University, Tsu, Mie 514‑8507, Japan
Published online on: November 7, 2014 https://doi.org/10.3892/br.2014.379
Pages: 88-92

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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 χ2 test 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 of ZPR1 was significantly associated (P=0.0012; odds ratio, 1.25; dominant model) with type 2 DM with the minor G allele representing a risk factor for this condition. Fasting plasma glucose levels (P=0.0076) and blood glycosylated hemoglobin contents (P=0.0132) significantly differed among ZPR1 genotypes with the G allele associated with increases in these parameters. ZPR1 may thus be a susceptibility locus for type 2 DM in Japanese individuals.

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