4p14区段和CTLA-4基因多态性与Graves病相关

Association of 4p14 and CTLA-4 gene polymorphisms with Graves' disease

目的探讨中国安徽蚌埠地区汉族人群4p14区段位点rs6832151和CTLA-4基因4个SNPs(单核苷酸多态性)位点基因多态性与Graves病相关性,和基因-基因交互作用对Graves病的影响。方法提取611例诊断明确的GD患者和644名健康对照者的全基因组DNA,用Taq Man探针技术进行基因分型,使用Plink和Haploview等统计软件分析这些位点与蚌埠地区汉族人群Graves病的相关性。结果 4p14区段位点rs6832151的等位基因、基因型频率在GD组和对照组之间有差异(P<0.05),CTLA-4基因区域内rs231804和rs231726两个SNP位点基因型在显性模型下差异显著(P<0.05);GMDR模型显示CTLA-4基因内rs10197319、rs231726、rs231804、rs1024161位点和4p14区段内rs6832151位点组成的五阶模型(P=0.001)为最佳模型,CTLA-4基因内rs1024161和rs10197319位点之间上位效应分析结果有差异(P<0.05)结论 4p14区段rs6832151,CTLA-4基因区域内rs231804和rs231726位点基因多态性与蚌埠地区汉族人群Graves病的遗传易感性相关;rs6832151(4p14区段)和rs10197319、rs231726、rs231804、rs1024161(CTLA-4基因)5个SNP位点间的基因-基因交互作用与Graves病相关,CTLA-4基因内rs1024161和rs10197319位点之间存在上位效应。

Objective To investigate the associations of the rs6832151 within chromosomal band 4p14 and four sin- gle-nucleotide polymorphisms （SNPs） in CTLA-4 gene with Graves＇ disease（GD）in a Chinese Han population from Bengbu city, Anhui province, as well as gene-gene interaction on Graves＇ disease. Methods A total of five SNPs were genotyped in a cohort of 611 GD patients and 644 healthy controls using TaqMan SNP genotyping .assay. The relation of these SNPs sites with GD was analyzed with Plink vl. 07 and Haploview 4. 0. Results An association was observed when the rs6832151 was directly analyzed or analyzed under three genetic models between GD and controls（P 〈 0. 05 ）. The frequencies of genotypes under dominant model of SNPs in CTLA-4（rs231804, rs231726）were significantly different between GD and controls. Gene-gene interactions among rs10197319, rs231726, rs231804, rs1024161 in CTLA-4 and rs6832151 in 4p14 on Graves＇ disease were significant （P =0. 001 ）. Signifi- Cant epistasis was found between rs1024161 and rs10197319 （ P 〈 0. 05 ）. Conclusions Polymorphism of the rs6832151 （4p14）, rs231804 and rs231726（CTLA-4） is a susceptible gene to Graves＇ disease in a Chinese Hart population from Bengbu city. A gene-gene interaction on Graves＇ disease is identified among rs10197319, rs231726, rs231804, rs1024161 （ CTLA- 4） and rs6832151 （4p14）. Epistatic interaction is observed between rs1024161 and rs10197319 in GD.