中国人CAPN10基因单核苷酸多态性的分布及其在北方汉族2型糖尿病人群中的关联分析

目的 检测始发现于墨西哥裔美国人群中的2型糖尿病易感基因CAPN10的苷酸多态性（single nucleotide polymorphism,SNP)在中国人群中的分布,并探讨其与中国北方汉族人群2型糖尿病的关联关系。方法 对27份取自中国不同民族人群DNA标本进行测序,以确定CAPN10基因中的SNP位点分布;选择其中5个位点,用单碱基延伸（single-extension,SBE)法对156例北方汉族正常人和173例2型糖尿病患者DNA标本进行SNP分型及病例－对照关联分析;对文献报道的易感基因CAPN10中的3个阳性位点进行单体型分析,并对其中1个位点在68个2型糖尿病家系（377例）中进行传递不平衡检验（transmission-disequilibrium test,TDT)和同胞传递不平衡检验（sib transmission-disequilibrium test,STDT）。结果 在所检测的8936bp长度范围内共检出40个SNP,平均约223bp1出现一个SNP,各多态性在基因中呈不均匀分布;中国人CAPN10的SNP与文献报道的墨西哥裔美国人群中该基因多态性存在较大的差异;所选择的5个SNP位点等位基因频率分布在正常人群和2型糖尿病患者间的差异无统计学意义（P＞0.05);上述3个阳性位点单体型频率在两组人群间差异无统计学意义（P＞0.05);TDT和STDT均无统计学意义（P＞0.05)。结论 CAPN10基因SNP具有民族差异;所检测的几个位点可能不是中国北方汉族2型糖尿病的主要易感基因位点。

Single nucleotide polymorphisms in CAPN10 gene of Chinese population and its correlation with type 2 diabetes mellitus in Han people of northern China

Objective To investigate the distribution of the single nucleotide polymorphisms (SNPs)in CAPN10gene in Chinese population and their relation with type2diabetes mellitus in Han people of Northern China.Methods CAPN10gene was sequenced to detect SNPs in27samples of different nationalities in China.5SNPs were genotyped with single-base extension(SBE)method to perform case-control study in156normal Han people of Northern China and173type2diabetes and the3positive loci reported in the article were performed haplotype analysis.One positive locus was also analyzed with transmission-disequilibrium test(TDT)and sib transmission-disequilibrium test(STDT)in68type2diabetes pedigrees(377cases).Results A total of40SNPs were identified in length of8936bp,with an average of1in every223bp;The SNPs in CAPN10gene did not distribute evenly and the SNPs in Chinese was different from that reported in American Mexicans.There was no significantly statistical difference in the allele frequency of the5SNPs between case and control(P>0.05),and the haplotype frequencies in the two groups were not much different (P>0.05).There was no positive results in TDT and STDT analysis(P>0.05).Conclusions The SNP distribution of CAPN10gene varies with different nationalities.The studied SNPs in CAPN10gene may not be the major susceptibility ones of type2diabetes mellitus in Han people of Northern China.