Replication of genome-wide association studies of type 2 diabetes susceptibility in Japan
Replication of genome-wide association studies of type 2 diabetes susceptibility in Japan
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DOI：
10.1210/jc.2008-0452
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发表时间：
2008-08-01
影响因子：
5.8
通讯作者：
Kasuga, Masato
中科院分区：
文献类型：
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作者：
Horikawa, Yukio;Miyake, Kazuaki;Kasuga, Masato
背景：在欧洲人和起源于欧洲的人群中，几个研究小组最近发现了新的2型糖尿病易感基因，包括FTO、SLC30A8、HHEX、CDKAL1、CDKN2B和IGF2BP2，这些基因都不在功能候选基因列表中。目的与设计：本研究的目的是利用相对较大的样本量在日本人群中复制先前发现的10个候选基因座内单核苷酸多态(SNPs)与2型糖尿病的关联：1921名2型糖尿病患者和1622名正常对照。结果：总共有15个SNP被分型。5个基因座的8个SNP与2型糖尿病相关：SLC30A8中rs3802177[优势比(OR)=1.16(95%可信区间1.05~1.27)；P=4.5×10(-3)]；HEX中rs1111875[OR=1.27(95%CI 1.14~1.40)；P=1.4×10(-5)]和rs7923837[OR=1.27(95%CI 1.13~1.43)；P=1.0 X10(-4)]；在CDKN2B中，rs10811661[OR=1.27(95%CI 1.15~1.40)；P=1.9×10(-6)]；在IGF2BP2中，rs4402960[OR=1.23(95%CI 1.11~1.36)；P=8.1X10(-5)]；rs1470579[OR=1.18(95%CI 1.07~1.31)；P=8.3×10(-4)]；以及rs7754840[OR=1.28(95%CI 1.17~1.41)]；P=4.5×10(-7)]和rs7756992[OR=1.27(95%CI 1.15-1.40)；P=9.8×10(-7)]。在CDKAL1和CDKN2B的变异中发现了第一和第二强关联，这两个变异都与胰岛β细胞的再生能力有关。结论：其中一些变异代表了日本和欧洲人常见的2型糖尿病易感基因。
Background: In Europeans and populations of European origin, several groups have recently identified novel type 2 diabetes susceptibility genes, including FTO, SLC30A8, HHEX, CDKAL1, CDKN2B, and IGF2BP2, none of which were in the list of functional candidates.Objective and Design: The aim of this study was to replicate in a Japanese population previously identified associations of single nucleotide polymorphisms (SNPs) within 10 candidate loci with type 2 diabetes using a relatively large sample size: 1921 subjects with type 2 diabetes and 1622 normal controls.Results: A total of 15 SNPs were genotyped. Eight SNPs in five loci were found to be associated with type 2 diabetes: rs3802177 [odds ratio (OR) = 1.16 (95% confidence interval (CI) 1.05-1.27); P = 4.5 X 10(-3)] in SLC30A8; rs1111875 [OR = 1.27 (95% CI 1.14-1.40); P = 1.4 X 10(-5)] and rs7923837 [OR = 1.27 (95% CI 1.13 - 1.43); P = 1.0 X 10(-4)] in HHEX; rs10811661 [OR = 1.27 (95% CI 1.15 - 1.40); P = 1.9 X 10(-6)] in CDKN2B; rs4402960 [OR = 1.23 ( 95% CI 1.11 - 1.36); P = 8.1 X 10(-5)] and rs1470579 [OR = 1.18 (95% CI 1.07 - 1.31); P = 8.3 X 10(-4)] in IGF2BP2; and rs7754840 [OR = 1.28 (95% CI 1.17 - 1.41); P = 4.5 X 10(-7)] and rs7756992 [OR = 1.27 ( 95% CI 1.15 - 1.40); P = 9.8 X 10(-7)] inCDKAL1. The first and second strongest associations were found at variants in CDKAL1 and CDKN2B, both of which are involved in the regenerative capacity of pancreatic beta-cells.Conclusion: Some of these variants represent common type 2 diabetes- susceptibility genes in both Japanese and Europeans.