2型糖尿病家系Calpain10基因多态性的研究

Study on Calpain10 gene polymorphism in Chinese type 2 diabetes families

目的 研究中国北方 2型糖尿病家系的Calpain10基因多态性 ,探讨其与 2型糖尿病发病的关系。方法 应用聚合酶链式反应 限制性内切酶长度多态性 (PCR RFLP)技术 ,对来自于 2 18个2型糖尿病家系中的 80 1个家系成员 ,2 11例无家族史的 2型糖尿病患者及 12 7例正常对照的Calpain10基因SNP4 3(G/A)及SNP19(1/2 )位点进行基因分型。结果 (1)SNP4 3位点G等位基因频率在无家族史的 2型糖尿病人群 (组 1)为 91 9% ,在 2型糖尿病家系先证者人群 (组 2 )为 92 7%、经连锁分析证实有连锁的 2型糖尿病家系先证者人群 (组 3)为 95 3% ,均高于正常对照组的 85 8%。统计学检验结果分别为 χ2 =6 39,df =1,P =0 0 11;χ2 =8 4 37,df=1,P <0 0 1;χ2 =16 4 9,df =1,P <0 0 1。但SNP19位点等位基因频率差异无显著意义。 (2 )Logistic回归分析 ,经性别、年龄和体重指数调整 ,提示SNP4 3G/G基因型与 2型糖尿病相关。 1、2、3病例组与对照组的回归分析结果分别为OR=1 78,P =0 0 4 5 ;OR =2 5 3,P =0 0 0 8;OR =4 32 ,P =0 0 0 0。结论 Calpain 10基因SNP4 3位点与 2型糖尿病相关 ,Calpain10基因可能为中国人 2型糖尿病的相关基因。

Objective To detect the Calpain10 gene polymorphisms in North China families with type 2 diabetes and to investigate their association with type 2 diabetes. Methods PCR-RFLP method was used to test the polymorphisms of Calpain10 SNP43 (G/A) and SNP19 (1/2) in 801 individuals from 218 type 2 diabetes mellitus (DM) families, 211 type 2 diabetes patients without family history, and 127 normal control subjects in northern China. Results (1) The Calpain 10 SNP43 ”G” allele frequency was 91.9% in the type 2 diabetic patients without family history, 92.7% in the probands from the type 2 diabetes families without linkage between the onset of DM and SNP43 site, and 95.3% in the probands from type 2 diabetes families with linkage evidence at SNP43, all significantly higher than that in the controls (85.8%, χ2=6.39,df=1,P=0.011;χ2=8.437,df=1, P<0.01); and χ2=16.49,df=1, P<0.01). The distribution of polymorphism of the SNP19 site was not significantly different between the patients and control subjects. (2) Logistic regression analysis adjusted by BMI, sex and age showed that SNP43 G/G genotype was associated with type 2 diabetes. The odds ratios of the three group were OR=1.78, P=0.045; OR =2.53,P=0.008; OR =4.32, P=0.000 respectively. Conclusion SNP43 site of Calpain10 gene is related to type 2 diabetes. Calpain 10 gene may be a related gene of type 2 diabetes in Chinese.