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Diabetes. 2009 Feb;58(2):493-8. doi: 10.2337/db07-1785. Epub 2008 Nov 25.

Replication study of candidate genes associated with type 2 diabetes based on genome-wide screening.

Author information

1
Department of Basic Medical Research and Education, Ehime University Graduate School of Medicine, Toon City, Ehime, Japan. tabara@m.ehime-u.ac.jp.

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.

PMID:
19033397
PMCID:
PMC2628625
DOI:
10.2337/db07-1785
[Indexed for MEDLINE]
Free PMC Article

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