Polymorphisms in the IDE-KIF11-HHEX gene locus are reproducibly associated with type 2 diabetes in a Japanese population
Polymorphisms in the IDE-KIF11-HHEX gene locus are reproducibly associated with type 2 diabetes in a Japanese population
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DOI：
10.1210/jc.2007-1029
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发表时间：
2008-01-01
影响因子：
5.8
通讯作者：
Nanjo, Kishio
中科院分区：
文献类型：
--
作者：
Furukawa, Yasushi;Shimada, Takeshi;Nanjo, Kishio
内容：法国人群的全基因组关联研究发现IDE-KIF 11-HHEX基因位点和SLC 30 A8基因位点的新单核苷酸多态性（SNPs）与2型糖尿病易感性相关。目的：我们调查这些位点的SNPs是否与日本人的2型糖尿病相关。设计：使用TaqMan基因分型分析系统对日本2型糖尿病患者（n = 405）和非糖尿病对照受试者（n = 340）中IDE-KIF 11-HHEX基因位点的两个SNP rs7923837和rs 1111875以及SLC 30 A8基因位点的一个SNP rs 13266634进行基因分型。rs7923837的G等位基因与2型糖尿病相关[比值比1.66，95%置信区间（CI）1.28-2.15; P = 0.00014]，遵循与先前报告的法国人群相同的趋势。与非携带者相比，风险等位基因的杂合子和纯合子携带者的优势比分别为1.57（95%CI 1.15-2.16; P= 0.0050）和3.16（95%CI 1.40-7.16; P= 0.0038）。虽然G等位基因在法国人群中为主要等位基因（66.5%），但在日本人群中为次要等位基因（23.8%）。rs 1111875的G等位基因也与2型糖尿病相关（优势比1.42，95%CI 1.13-1.78; P = 0.0024）。与非携带者相比，风险等位基因的杂合子和纯合子携带者的优势比分别为1.31（95%CI 0.97-1.77; P = 0.0810）和2.40（95%CI 1.34-4.32; P = 0.0028）。结论：IDE-KIF 11-HHEX基因多态性与2型糖尿病易感性存在种族差异。
Context: A genome-wide association study in the French population has detected that novel single-nucleotide polymorphisms (SNPs) in the IDE-KIF11-HHEX gene locus and the SLC30A8 gene locus are associated with susceptibility to type 2 diabetes.Objective: We investigated whether SNPs in these loci were associated with type 2 diabetes in Japanese.Design: Two SNPs, rs7923837 and rs1111875, in the IDE-KIF11-HHEX gene locus and one SNP, rs13266634, in the SLC30A8 gene locus were genotyped in Japanese type 2 diabetic patients (n 405) and in nondiabetic control subjects (n = 340) using the TaqMan genotyping assay system.Results: The G allele of rs7923837 was associated with type 2 diabetes [odds ratio 1.66, 95% confidence interval (CI) 1.28-2.15; P = 0.00014], following the same tendency as in the French population of the previous report. Heterozygous and homozygous carriers of the risk allele had odds ratios of 1.57 (95% CI 1.15-2.16; P= 0.0050)and 3.16(95% CI 1.40-7.16; P= 0.0038) relative to noncarriers. Although the G allele was a major allele (66.5%) in the French population, it was a minor allele (23.8%) in Japanese. The G allele of rs1111875 was also associated with type 2 diabetes (odds ratio 1.42, 95% CI 1.13-1.78; P = 0.0024). Heterozygous and homozygous carriers of the risk allele had odds ratios of 1.31 (95% CI 0.97-1.77; P = 0.0810) and 2.40 (95% CI 1.34-4.32; P = 0.0028) relative to noncarriers. A significant association with type 2 diabetes was not observed for rs13266634.Conclusions: Polymorphisms in the IDE-KIF11-HHEX gene locus are associated with susceptibility to type 2 diabetes across the boundary of race.