A single nucleotide polymorphism within DUSP9 is associated with susceptibility to type 2 diabetes in a Japanese population.
A single nucleotide polymorphism within DUSP9 is associated with susceptibility to type 2 diabetes in a Japanese population.
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DOI：
10.1371/journal.pone.0046263
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Maeda S
中科院分区：
文献类型：
--
作者：
Fukuda H;Imamura M;Tanaka Y;Iwata M;Hirose H;Kaku K;Maegawa H;Watada H;Tobe K;Kashiwagi A;Kawamori R;Maeda S
在欧洲全基因组关联研究（GWAS）的荟萃分析中，X染色体上的DUSP9位点被确定为2型糖尿病的易感性位点，南亚人群的GWAS发现了6个额外的2型糖尿病单核苷酸多态性（SNP）位点。然而，这些基因位点与2型糖尿病的关系尚未在日本人身上得到检验。我们进行了一项重复性研究，以调查日本人群中这7个易感基因位点与2型糖尿病的关系。我们对7个snp （DUSP9附近的rss5945326， GRB14附近的rs3923113， ST6GAL1附近的rs16861329， VPS26A附近的rs1802295， HMG20A附近的rs7178572， AP3S2附近的rs2028299， hnf4a附近的rs4812829）中的每一个进行了11,319名日本参与者（8,318名2型糖尿病患者和3,001名对照）的基因分型，并通过逻辑回归分析检测了这7个snp与2型糖尿病的关系。所有snp的影响方向与原始报道相同（优势比[OR] bbb1.0）。DUSP9附近的一个SNP rs5945326与2型糖尿病在全基因组显著性水平上显著相关（p = 2.21×10−8;OR 1.39, 95%可信区间[CI]: 1.24−1.56）。来自南亚GWAS的6个snp本身与日本人群的2型糖尿病没有显著相关性（p≥0.007）。然而，由6个南亚GWAS衍生snp构建的遗传风险评分与日本2型糖尿病显著相关（p = 8.69×10−4,OR = 1.06）。95%可信区间;1.03−1.10)。这些结果表明，DUSP9位点是不同种族2型糖尿病的共同易感位点，南亚GWAS中发现的6个位点也对日本2型糖尿病的易感性有显著影响。
The DUSP9 locus on chromosome X was identified as a susceptibility locus for type 2 diabetes in a meta-analysis of European genome-wide association studies (GWAS), and GWAS in South Asian populations identified 6 additional single nucleotide polymorphism (SNP) loci for type 2 diabetes. However, the association of these loci with type 2 diabetes have not been examined in the Japanese. We performed a replication study to investigate the association of these 7 susceptibility loci with type 2 diabetes in the Japanese population. We genotyped 11,319 Japanese participants (8,318 with type 2 diabetes and 3,001 controls) for each of the 7 SNPs–rs5945326 near DUSP9, rs3923113 near GRB14, rs16861329 in ST6GAL1, rs1802295 in VPS26A, rs7178572 in HMG20A, rs2028299 near AP3S2, and rs4812829 in HNF4A–and examined the association of each of these 7 SNPs with type 2 diabetes by using logistic regression analysis. All SNPs had the same direction of effect (odds ratio [OR]>1.0) as in the original reports. One SNP, rs5945326 near DUSP9, was significantly associated with type 2 diabetes at a genome-wide significance level (p = 2.21×10−8; OR 1.39, 95% confidence interval [CI]: 1.24−1.56). The 6 SNPs derived from South Asian GWAS were not significantly associated with type 2 diabetes in the Japanese population by themselves (p≥0.007). However, a genetic risk score constructed from 6 South Asian GWAS derived SNPs was significantly associated with Japanese type 2 diabetes (p = 8.69×10−4, OR = 1.06. 95% CI; 1.03−1.10). These results indicate that the DUSP9 locus is a common susceptibility locus for type 2 diabetes across different ethnicities, and 6 loci identified in South Asian GWAS also have significant effect on susceptibility to Japanese type 2 diabetes.
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作者：
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通讯作者：
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