部分基因组扫描研究2型糖尿病易感基因座位的初步报告

A genome scan for late onset type-2 diabetes susceptibility loci in Chinese: a preliminary report

目的 通过部分基因组扫描筛查与 2型糖尿病连锁的位点 ,为进一步定位和克隆 2型糖尿病的易感基因奠定基础。方法 采用以微卫星DNA标记为基础的荧光标记 半自动基因组扫描技术 ,应用Perkin Elmer的试剂盒 (ABIPrismLinkageMappingSetVersion 2 ) ,共 6 3对引物 ,研究 2型糖尿病家系 5 8个 ,共 2 6 4份样品 ,其中糖尿病患者 15 2人 ,非糖尿病患者 112人 ,有同胞关系的患者74人 ,组成 45对患病同胞对 ,对 1号、12号、18号、2 0号染色体进行部分基因组扫描。连锁分析采用GENEHUNTERversion 2连锁分析软件包。结果 非参数连锁分析结果提示 ,1号染色体 1p31区域的D1S2 86 8位点同 2型糖尿病连锁 ,其NPL值为 1.192 ,P值为 0 .0 45 ,2 0号染色体短臂末端 2 0 p13区域的位点D2 0S117和D2 0S889以及 2 0号染色体长臂 2 0q13 .3区域的D2 0S196位点同 2型糖尿病连锁 ,其NPL值分别为 1.36 2、1.36 0、1.199,P值分别为 0 .0 30、0 .0 30和 0 .0 49。结论 1号染色体短臂 1p31区域及 2 0号染色体短臂 2 0 p13区域及长臂 2 0 q13.3区域可能存在有 2型糖尿病的易感基因。

Objective To identify loci influencing susceptibility to late onset type 2 diabetes mellitus by genome scan method. Methods Genome scan method based on fluorescence labeled microsatellite markers with multiplex PCR system was used to identify loci influencing susceptibility to late onset type 2 diabetes mellitus. The 63 pairs of primers of microsatellits DNA markers used in this study were provided by Perkin Elmer Applied Biosystems Division. 264 samples from 58 pedigrees were studied. Among these samples, 152 were collected from diabetic patients including 74 affected siblings forming 45 affected sib pairs and 112 from non diabetic members. Chromosome 1, 12, 18, 20 were scanned and linkage analysis were carried out with GENEHUNTER (version 2) software. Results Non parametric linkage analysis showed evidence for linkage at several chromosome regions with type 2 diabetes mellitus, including D1S2868 at 1p31, with NPL value of 1.192 and p value of 0.045, and D20S177, D20S889, D20S196 at 20p13, 20p13 and 20q13.3 respectively, withNPL valueof1.362,1.360,and 1.199 respectively and p value of 0.030, 0.030 and 0.049 respectively. Conclusion Loci on region 1p31, 20p13 and 20q13.3 may influence susceptibility to type 2 diabetes.