PPARG, KCNJ11, CDKAL1, CDKN2A-CDKN2B, IDE-KIF11-HHEX, IGF2BP2 and SLC30A8 are associated with type 2 diabetes in a Chinese population.
PPARG, KCNJ11, CDKAL1, CDKN2A-CDKN2B, IDE-KIF11-HHEX, IGF2BP2 and SLC30A8 are associated with type 2 diabetes in a Chinese population.
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PPARG、KCNJ11、CDKAL1、CDKN2A-CDKN2B、IDE-KIF11-HHEX、IGF2BP2 和 SLC30A8 与中国人群的 2 型糖尿病相关
DOI：
10.1371/journal.pone.0007643
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发表时间：
2009-10-28
期刊：
影响因子：
3.7
通讯作者：
Jia W
中科院分区：
文献类型：
--
作者：
Hu C;Zhang R;Wang C;Wang J;Ma X;Lu J;Qin W;Hou X;Wang C;Bao Y;Xiang K;Jia W
背景近年来遗传学研究的进展使2型糖尿病的易感基因增加到18个。在本研究中，我们试图分析来自这些位点的变异对2型糖尿病和与糖代谢相关的临床表型的独立和联合作用。方法/主要发现来自14个位点的21个单核苷酸多态性（SNP）在1，849例2型糖尿病患者和1，785例正常血糖调节者中成功进行基因分型。我们分析了这些SNPs在病例组和对照组之间的等位基因和基因型分布，以及易感基因座对2型糖尿病风险的联合作用。用Logistic回归分析SNPs与2型糖尿病的关系。通过线性回归分析SNPs与数量性状的相关性。通过受试者工作特征曲线下面积评估预测模型的判别准确性。我们证实了PPARG、KCNJ 11、CDKAL 1、CDKN 2A-CDKN 2B、IDE-KIF 11-HHEX、IGF 2BP 2和SLC 30 A8的SNP对2型糖尿病风险的影响，比值比范围为1.114至1.406（P值范围为0.0335至1.37E-12）。但未检测到WFS 1、FTO、JAZF 1、TSPAN 8-LGR 5、THADA、ADAMTS 9、NOTCH 2-ADAM 30的SNPs与2型糖尿病的关联。对对照组的数量性状分析表明，THADA SNP rs7578597与口服葡萄糖耐量试验中的2小时胰岛素相关（P = 0.0005，经验P = 0.0090）。 11个位点的SNPs联合效应分析显示，携带危险等位基因越多的个体患2型糖尿病的风险越高。携带危险等位基因的2型糖尿病患者诊断年龄较早（P = 0.0006）。 结论：PPARG、KCNJ 11、CDKAL 1、CDKN 2A-CDKN 2B、IDE-KIF 11-HHEX、IGF 2BP 2和SLC 30 A8与2型糖尿病的关系。这些2型糖尿病危险基因座对疾病的贡献是累加的。
Background Recent advance in genetic studies added the confirmed susceptible loci for type 2 diabetes to eighteen. In this study, we attempt to analyze the independent and joint effect of variants from these loci on type 2 diabetes and clinical phenotypes related to glucose metabolism. Methods/Principal Findings Twenty-one single nucleotide polymorphisms (SNPs) from fourteen loci were successfully genotyped in 1,849 subjects with type 2 diabetes and 1,785 subjects with normal glucose regulation. We analyzed the allele and genotype distribution between the cases and controls of these SNPs as well as the joint effects of the susceptible loci on type 2 diabetes risk. The associations between SNPs and type 2 diabetes were examined by logistic regression. The associations between SNPs and quantitative traits were examined by linear regression. The discriminative accuracy of the prediction models was assessed by area under the receiver operating characteristic curves. We confirmed the effects of SNPs from PPARG, KCNJ11, CDKAL1, CDKN2A-CDKN2B, IDE-KIF11-HHEX, IGF2BP2 and SLC30A8 on risk for type 2 diabetes, with odds ratios ranging from 1.114 to 1.406 (P value range from 0.0335 to 1.37E-12). But no significant association was detected between SNPs from WFS1, FTO, JAZF1, TSPAN8-LGR5, THADA, ADAMTS9, NOTCH2-ADAM30 and type 2 diabetes. Analyses on the quantitative traits in the control subjects showed that THADA SNP rs7578597 was association with 2-h insulin during oral glucose tolerance tests (P = 0.0005, empirical P = 0.0090). The joint effect analysis of SNPs from eleven loci showed the individual carrying more risk alleles had a significantly higher risk for type 2 diabetes. And the type 2 diabetes patients with more risk allele tended to have earlier diagnostic ages (P = 0.0006). Conclusions/Significance The current study confirmed the association between PPARG, KCNJ11, CDKAL1, CDKN2A-CDKN2B, IDE-KIF11-HHEX, IGF2BP2 and SLC30A8 and type 2 diabetes. These type 2 diabetes risk loci contributed to the disease additively.