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- Title
SNPs in the KCNJ11- ABCC8 gene locus are associated with type 2 diabetes and blood pressure levels in the Japanese population.
- Authors
Sakamoto, Yukiko; Inoue, Hiroshi; Keshavarz, Parvaneh; Miyawaki, Katsuyuki; Yamaguchi, Yuka; Moritani, Maki; Kunika, Kiyoshi; Nakamura, Naoto; Yoshikawa, Toshikazu; Yasui, Natsuo; Shiota, Hiroshi; Tanahashi, Toshihito; Itakura, Mitsuo
- 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.
- Subjects
TYPE 2 diabetes; BLOOD pressure; GENETICS of diabetes; GENETIC polymorphisms; VITAL signs; HUMAN population genetics; GENETIC research; JAPANESE people; DISEASES
- Publication
Journal of Human Genetics, 2007, Vol 52, Issue 10, p781
- ISSN
1434-5161
- Publication type
Article
- DOI
10.1007/s10038-007-0190-x