通过目标区域测序寻找新的自身免疫性甲状腺疾病候选基因及相关位点  

Search for New Autoimmune Thyroid Disease Candidate Genes and Related Loci by Target Region Sequencing

作　　者：狄立强 李素丽[2] 张洁[2] 吉米兰木·麦麦提明[2] 罗蕴之[2] 郭艳英 DI Liqiang;LI Suli;ZHANG Jie;Jimilanmu·MAIMAITIMING;LUO Yunzhi;GUO Yanying(School of Life Sciences and Technology,Xinjiang University,Urumqi,830046;Department of Endocrine and Metabolic Diseases,People′s Hospital of Xinjiang Uygur Autonomous Region,Xinjiang Diabetes Clinical Medical Research Center,Urumqi,830001)

机构地区：[1]新疆大学生命科学与技术学院,乌鲁木齐830046 [2]新疆维吾尔自治区人民医院内分泌与代谢病科,新疆糖尿病临床医学研究中心,乌鲁木齐830001

出　　处：《基因组学与应用生物学》2024年第1期172-180,共9页Genomics and Applied Biology

基　　金：国家自然科学基金项目(81860148)资助。

摘　　要：自身免疫性甲状腺疾病(autoimmune thyroid disease,AITD)是一种主要由T细胞介导的器官特异性自身免疫性疾病,包括格雷夫斯病(Graves disease,GD)和桥本甲状腺炎(Hashimoto thyroiditis,HT),其发病率与遗传因素紧密相关。本研究旨在确定与AITD相关的易感基因及位点。本研究通过对100例AITD(51例HT和49例GD)患者和50例健康体检者的基因组进行目标区域测序,并对基因多态性与AITD之间的相关性进行了统计学分析,进一步进行连锁分析找到易感基因及相关位点。本研究发现了BACH2基因的5个单核苷酸多态性(single nucleotide polymorphism,SNP)位点(rs12205059、rs62408219、rs7742121、rs7756574、rs12204886)完全连锁,ARID5B基因10个SNP位点(rs12778514、rs3740354、rs3740353、rs9633555、rs9633557、rs9633534、rs3740352、rs2393730、rs2393729、rs2393728)连锁程度较高,NFKB1基因7个SNP位点(rs230528、rs230526、rs230521、rs230517、rs230512、rs4648011、rs230505)连锁程度较高,它们显示与GD显著相关;BACH2基因24个SNP位点(rs77175037、rs16882370、rs77758469、rs78777913、rs117721419、rs78336372、rs76671310、rs76587383、rs75249386、rs79815784、rs57765055、rs75199762、rs75340880、rs9444735、rs61246723、rs9451336、rs78318422、rs117023048、rs74639869、rs75487886、rs80029445、rs78252829、rs60148132、rs58745003)完全连锁,以及4个SNP位点(rs60519986、rs56835438、rs58205153、rs9451298)连锁程度较高,显示与HT显著相关;BACH2基因4个SNP位点(rs12205059、rs7742121、rs7756574、rs12204886)连锁程度较高,ARID5B基因5个SNP位点(rs9633555、rs9633556、rs2393730、rs2393729、rs2393728)连锁程度较高,它们与GD和HT易感性均显著相关。本研究揭示了BACH2、ARID5B和NFKB1基因的多态性与AITD易感性有关,它们可能参与了AITD的发病机制。Autoimmune thyroid disease(AITD)is an organ-specific autoimmune disease mainly mediated by T cells,including Graves disease(GD)and Hashimoto thyroiditis(HT).The incidence of AITD is closely related to genetic factors.The aim of this study is identifying susceptibility genes and loci associated with AITD.In this study,the genomes of 100 patients with AITD(51 HT and 49 GD)and 50 healthy subjects were sequenced in targeted regions,and the correlation between gene polymorphisms and AITD was statistically analyzed,and further linkage analysis was performed to find susceptibility genes and associated loci in genes.In this study,five SNP loci(rs12205059,rs62408219,rs7742121,rs7756574,rs12204886)in BACH2 gene were found to be completely linked,ten SNP loci(rs12778514,rs3740354,rs3740353,rs9633555,rs9633557,rs9633534,rs3740352,rs2393730,rs2393729,rs2393728)in ARID5B gene were highly linked,seven SNP loci(rs230528,rs230526,rs230521,rs230517,rs230512,rs4648011,rs230505)in NFKB1 gene were highly linked,and they showed significant correlation with GD;twenty-four SNP loci(rs77175037,rs16882370,rs77758469,rs78777913,rs117721419,rs78336372,rs76671310,rs76587383,rs75249386,rs79815784,rs57765055,rs75199762,rs75340880,rs9444735,rs61246723,rs9451336,rs78318422,rs117023048,rs74639869,rs75487886,rs80029445,rs78252829,rs60148132,rs58745003)in BACH2 gene were completely linked,and four SNP loci(rs60519986,rs56835438,rs58205153,rs9451298)were highly linked,showing significant correlation with HT;four SNP loci(rs12205059,rs7742121,rs7756574,rs12204886)in BACH2 gene were highly linked,and five SNP loci(rs9633555,rs9633556,rs2393730,rs2393729,rs2393728)in ARID5B gene were highly linked,and they all showed significant association with GD and HT susceptibility.This study reveals that the polymorphisms of BACH2,ARID5B and NFKB1 genes are associated with AITD susceptibility,and they may be involved in the pathogenesis of AITD.

关 键 词：自身免疫性甲状腺疾病 格雷夫斯病 桥本甲状腺炎 连锁分析 单核苷酸多态性(SNP) 

分 类 号：R581[医药卫生—内分泌]