福建籍汉族人系统性红斑狼疮的单核苷酸多态性分析

Single Nucleotide Polymorphism Analysis of Systemic Lupus Erythematosus(in Fujian Han Population)

目的筛选系统性红斑狼疮(SLE)遗传易感基因,发现新的易感SNP位点。方法采用SNP基因芯片与DNA池相结合(SNP microarrays and DNA pools,SNP-MaP),在福建籍汉族人群中对240例SLE患者和210例正常对照DNA池分别进行全基因组扫描,通过正态分布法估计正常对照和SLE患者DNA池SNP-MaP等位基因频率,用DNA池测序法验证杂合度,用TaqMan法验证单个样本。结果筛选出108个新的SLE候选易感基因,验证了其中的6个新的易感SNP位点的杂合度,结果与SNP基因芯片结果基本一致,证实rs4731117为一个新发现的易感位点。结论 SNP基因芯片与DNA池相结合的方法是一个实用性好的高通量的SNP筛选工具。rs4731117位点多态性与福建籍汉族人群SLE发病的易感性有一定关系。

Objective To identify new susceptibility loci by screening susceptibility genes for human Systemic Lupus Erythematosus（SLE）.Methods In Fujian Han population,240 SLE patients and 210 controls were employed in the study.The difference of allelic ratio of SNP in patients and controls was assayed by a high throughput method（combining DNA-pooling and microarray,SNP-MaP）.The heterozygosity was further validated by DNA-sequencing.The samples were individually genotyped by real-time PCR（Taqman）.Results A total of 108 SNPs was screened to be candidate genetic susceptibility loci for SLE,of which 6 SNPs were further validated.The results of DNA-sequencing were consistent with those of SNP-MaP.One SNP,rs4731117,was confirmed to be a new genetic susceptibility site for SLE.Conclusion A new method combining SNP microarray and DNA-pooling（SNP-MaP） has been developed to be a high throughout and effective tool.The polymorphism of rs4731117 may be associated with the susceptibility to SLE in Fujian Han population.