Investigation of type 2 diabetes risk alleles support CDKN2A/B, CDKAL1, and TCF7L2 as susceptibility genes in a Han Chinese cohort.
Investigation of type 2 diabetes risk alleles support CDKN2A/B, CDKAL1, and TCF7L2 as susceptibility genes in a Han Chinese cohort.
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DOI：
10.1371/journal.pone.0009153
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发表时间：
2010-02-10
期刊：
影响因子：
3.7
通讯作者：
Hu R
中科院分区：
文献类型：
--
作者：
Wen J;Rönn T;Olsson A;Yang Z;Lu B;Du Y;Groop L;Ling C;Hu R
最近的全基因组关联研究(GWAS)已经报道了几个与2型糖尿病有重复相关的基因变异。在欧洲血统的人群中对三个GWAS进行的荟萃分析中也发现了其他的变异。在这项研究中，我们评估了来自15个候选基因座的17个遗传变异在中国汉族人群中的影响，这些候选基因座在2型糖尿病GWASs和荟萃分析中被识别。对1165例2型糖尿病患者和1136例正常血糖对照人群进行了2型糖尿病相关基因变异的基因分型。根据年龄、性别和BMI调整后的Logistic回归模型计算发生2型糖尿病的风险比。用多元线性回归模型检验了基因型与表型的相关性。CDKN2A/B、CDKAL1、TCF7L2、TCF2、MC4R和PPARG基因变异与2型糖尿病有名义上的关联(P≤0.0 5)，其中CDKN2 A/B rs10 811661，OR：1.2 6(1.12-1.43)P = 1.8*10−4；CDKAL1 rs10 946398，OR：1.2 3(1.09-1.39)；仅观察到 = 的rs8050136与糖尿病组的空腹血糖(P−0.002)、餐后血糖(P = 0.002)、空腹C肽水平(P = 0.006)以及对照组的体重指数(P = 0.033)存在名义表型关联。我们在中国汉族人群中发现了CDKN2A/B、CDKAL1和TCF7L2基因变异与2型糖尿病之间的显著关联，表明这些基因是不同种族的2型糖尿病易感性的有力候选基因。
Recent genome-wide association studies (GWASs) have reported several genetic variants to be reproducibly associated with type 2 diabetes. Additional variants have also been detected from a metaanalysis of three GWASs, performed in populations of European ancestry. In the present study, we evaluated the influence of 17 genetic variants from 15 candidate loci, identified in type 2 diabetes GWASs and the metaanalysis, in a Han Chinese cohort. Selected type 2 diabetes–associated genetic variants were genotyped in 1,165 type 2 diabetic patients and 1,136 normoglycemic control individuals of Southern Han Chinese ancestry. The OR for risk of developing type 2 diabetes was calculated using a logistic regression model adjusted for age, sex, and BMI. Genotype-phenotype associations were tested using a multivariate linear regression model. Genetic variants in CDKN2A/B, CDKAL1, TCF7L2, TCF2, MC4R, and PPARG showed a nominal association with type 2 diabetes (P≤0.05), of whom the three first would stand correction for multiple testing: CDKN2A/B rs10811661, OR: 1.26 (1.12–1.43) P = 1.8*10−4; CDKAL1 rs10946398, OR: 1.23 (1.09–1.39); P = 7.1*10−4, and TCF7L2 rs7903146, OR: 1.61 (1.19–2.18) P = 2.3 * 10−3. Only nominal phenotype associations were observed, notably for rs8050136 in FTO and fasting plasma glucose (P = 0.002), postprandial plasma glucose (P = 0.002), and fasting C-peptide levels (P = 0.006) in the diabetic patients, and with BMI in controls (P = 0.033). We have identified significant association between variants in CDKN2A/B, CDKAL1 and TCF7L2, and type 2 diabetes in a Han Chinese cohort, indicating these genes as strong candidates conferring susceptibility to type 2 diabetes across different ethnicities.
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作者：
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通讯作者：
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影响因子：
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作者：
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Frayling, TM