Volume 52, Number 10, 781-793, DOI: 10.1007/s10038-007-0190-x

SNPs in the KCNJ11 - ABCC8 gene locus are associated with type 2 diabetes and blood pressure levels in the Japanese population

Yukiko Sakamoto, Hiroshi Inoue, Parvaneh Keshavarz, Katsuyuki Miyawaki, Yuka Yamaguchi, Maki Moritani, Kiyoshi Kunika, Naoto Nakamura, Toshikazu Yoshikawa and Natsuo Yasui, et al.

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Abstract

Many genetic association studies support a contribution of genetic variants in the KCNJ11-ABCC8 gene locus to type 2 diabetes (T2D) susceptibility in Caucasians. In non-Caucasian populations, however, there have been only a few association studies, and discordant results were obtained. Herein, we selected a total of 31 SNPs covering a 211.3-kb region of the KCNJ11-ABCC8 locus, characterized the patterns of linkage disequilibrium (LD) and haplotype structure, and performed a case-control association study in a Japanese population consisting of 909 T2D patients and 893 control subjects. We found significant associations between eight SNPs, including the KCNJ11 E23K and ABCC8 S1369A variants, and T2D. These disease-associated SNPs were genetically indistinguishable because of the presence of strong LD, as found previously in Caucasians. For the KCNJ11 E23K variant, the most significant association was obtained under a dominant genetic model (OR 1.32, 95% CI 1.09–1.60, P = 0.004). A meta-analysis of East Asian studies, comprising a total of 3,357 T2D patients (77.4% Japanese) and 2,836 control subjects (77.8% Japanese), confirmed the significant role of the KCNJ11 E23K variant in T2D susceptibility. Furthermore, we found evidence suggesting that the KCNJ11 E23K genotype is independently associated with higher blood-pressure levels.

Keywords  Type 2 diabetes -  KCNJ11  -  ABCC8  - Genetic association study - Japanese population - Blood pressure

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