Replication Study of Candidate Genes Associated With Type 2 Diabetes Based On Genome-Wide Screening
Author:
Tabara Yasuharu1, Osawa Haruhiko2, Kawamoto Ryuichi3, Onuma Hiroshi2, Shimizu Ikki4, Miki Tetsuro5, Kohara Katsuhiko5, Makino Hideichi2
Affiliation:
1. Department of Basic Medical Research and Education, Ehime University Graduate School of Medicine, Toon City, Ehime, Japan 2. Department of Molecular and Genetic Medicine, Ehime University Graduate School of Medicine, Toon City, Ehime, Japan 3. Department of Internal Medicine, Seiyo City Nomura Hospital, Seiyo City, Ehime, Japan 4. Department of Internal Medicine, Ehime Prefectural Hospital, Toon City, Ehime, Japan 5. Department of Geriatric Medicine, Ehime University Graduate School of Medicine, Toon City, Ehime, Japan
Abstract
OBJECTIVE—The present study was conducted to confirm possible associations between candidate genes from genome-wide association studies and type 2 diabetes in Japanese diabetic patients and a community-based general population. A total of 11 previously reported single-nucleotide polymorphisms (SNPs) from the TCF7L2, CDKAL1, HHEX, IGF2BP2, CDKN2A/B, SLC30A8, and KCNJ11 genes were analyzed.
RESEARCH DESIGN AND METHODS—Candidate SNPs were genotyped in 506 type 2 diabetic patients and 402 control subjects and meta-analyzed with six previous association studies in Japanese patients. Associations with fasting plasma insulin levels were investigated in a general population sample (n = 1,963, 61 ± 13 years).
RESULTS—In our case-control subjects, susceptibility to type 2 diabetes was replicated in TCF7L2 (rs12255372), CDKAL1 (rs7756992, rs7754840), HHEX (rs7923837), IGF2BP2 (rs4402960 and rs1470579), CDKN2A/B (rs10811661), and SLC30A8 (rs13266634). In addition to these polymorphisms, meta-analysis confirmed the association of type 2 diabetes susceptibility with KCNJ11 rs5219, TCF7L2 rs7903146, and HHEX rs1111875. The TCF7L2 rs12255372 polymorphism showed the highest odds ratio (OR) for type 2 diabetes (OR 1.714 [1.298–2.263]). Odds ratio of other polymorphisms ranged from 1.13 to 1.41. The risk allele of CDKAL1 rs7756992 was significantly associated with lower insulin levels in type 2 diabetic patients after adjustment for other confounding factors.
CONCLUSIONS—Type 2 diabetes susceptibility of seven candidate genes was confirmed in Japanese. Conservation of susceptible loci for type 2 diabetes was independent of ethnic background.
Publisher
American Diabetes Association
Subject
Endocrinology, Diabetes and Metabolism,Internal Medicine
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