中华内分泌代谢杂志
中華內分泌代謝雜誌
중화내분비대사잡지
CHINESE JOURNAL OF ENDOCRINOLOGY AND METABOLISM
2012年
7期
565-569
,共5页
孙媛媛%杜文华%梁翠格%刘晓萌%李守杰%李文侠%董庆玉%王月丽%刘炳丽%宋怀东%高冠起
孫媛媛%杜文華%樑翠格%劉曉萌%李守傑%李文俠%董慶玉%王月麗%劉炳麗%宋懷東%高冠起
손원원%두문화%량취격%류효맹%리수걸%리문협%동경옥%왕월려%류병려%송부동%고관기
格雷夫斯病%促甲状腺素受体%内含子%多态性,单核苷酸%促甲状腺激素受体抗体
格雷伕斯病%促甲狀腺素受體%內含子%多態性,單覈苷痠%促甲狀腺激素受體抗體
격뢰부사병%촉갑상선소수체%내함자%다태성,단핵감산%촉갑상선격소수체항체
Graves' disease%TSHR%Intron%Polymorphisms,single nucleotide%TSH receptor antibody
目的 探讨中国山东临沂地区汉族人群促甲状腺素受体( TSHR)基因内含子1区域单核苷酸多态性(SNP)与Graves病的关系.方法 应用全基因组关联研究(GWAS)和TaqMan探针技术,对1759例GD患者和1740名健康对照者TSHR内含子1区域进行基因分型；同时检测甲状腺激素水平及促甲状腺激素受体抗体(TRAb)水平.结果 选取GWAS研究中发现的5个SNPs位点进入扩大样本的验证,发现rs12101261_T与GD关联性较强(OR=1.257,95％ CI.1.137～1.390,P=8.23× 10-6),logistic回归分析显示rs12101261是GD一个独立致病位点(P=1.61×10-3)；rs12101261_T与治疗1年后TRAb阳性的患者显著相关(OR=1.317,95％CI 1.171～1.481,P=4.14×10-4),与TRAb阴性者无相关性(OR=1.056,95％CI0.892～1.251,P=0.524).rs12101261的3种基因型在TRAb阳性和阴性组的分布差异有统计学意义(P=0.014),其他临床表现差异均无统计学意义(P＞0.05).结论 TSHR基因内含子1区域5个SNP与山东临沂地区汉族人群GD相关,其中rs12101261是一个独立致病位点,该基因多态性与血清TRAb水平相关.
目的 探討中國山東臨沂地區漢族人群促甲狀腺素受體( TSHR)基因內含子1區域單覈苷痠多態性(SNP)與Graves病的關繫.方法 應用全基因組關聯研究(GWAS)和TaqMan探針技術,對1759例GD患者和1740名健康對照者TSHR內含子1區域進行基因分型；同時檢測甲狀腺激素水平及促甲狀腺激素受體抗體(TRAb)水平.結果 選取GWAS研究中髮現的5箇SNPs位點進入擴大樣本的驗證,髮現rs12101261_T與GD關聯性較彊(OR=1.257,95％ CI.1.137～1.390,P=8.23× 10-6),logistic迴歸分析顯示rs12101261是GD一箇獨立緻病位點(P=1.61×10-3)；rs12101261_T與治療1年後TRAb暘性的患者顯著相關(OR=1.317,95％CI 1.171～1.481,P=4.14×10-4),與TRAb陰性者無相關性(OR=1.056,95％CI0.892～1.251,P=0.524).rs12101261的3種基因型在TRAb暘性和陰性組的分佈差異有統計學意義(P=0.014),其他臨床錶現差異均無統計學意義(P＞0.05).結論 TSHR基因內含子1區域5箇SNP與山東臨沂地區漢族人群GD相關,其中rs12101261是一箇獨立緻病位點,該基因多態性與血清TRAb水平相關.
목적 탐토중국산동림기지구한족인군촉갑상선소수체( TSHR)기인내함자1구역단핵감산다태성(SNP)여Graves병적관계.방법 응용전기인조관련연구(GWAS)화TaqMan탐침기술,대1759례GD환자화1740명건강대조자TSHR내함자1구역진행기인분형；동시검측갑상선격소수평급촉갑상선격소수체항체(TRAb)수평.결과 선취GWAS연구중발현적5개SNPs위점진입확대양본적험증,발현rs12101261_T여GD관련성교강(OR=1.257,95％ CI.1.137～1.390,P=8.23× 10-6),logistic회귀분석현시rs12101261시GD일개독립치병위점(P=1.61×10-3)；rs12101261_T여치료1년후TRAb양성적환자현저상관(OR=1.317,95％CI 1.171～1.481,P=4.14×10-4),여TRAb음성자무상관성(OR=1.056,95％CI0.892～1.251,P=0.524).rs12101261적3충기인형재TRAb양성화음성조적분포차이유통계학의의(P=0.014),기타림상표현차이균무통계학의의(P＞0.05).결론 TSHR기인내함자1구역5개SNP여산동림기지구한족인군GD상관,기중rs12101261시일개독립치병위점,해기인다태성여혈청TRAb수평상관.
Objective To investigate the association between single nucleotide polymorphisms in the intron 1 of thyroid stimnulating hormone receptor gene (TSHR) and Graves' disease (GD) in the Chinese Han population from Linyi city,Shandong Province.Methods A total of 1759 GD patients and 1740 control subjects were recruited for genotyping in TSHR intron 1 with genome-wide association study (GWAS) and Taqman probe technique.At the same time,serum thyroid hormone and TSH receptor antibody (TRAb) levels of patients were determined.Results Five SNPs were selected for further replication.The rs12101261 _T was significantly associated with GD risk ( OR=1.257,95％CI 1.137-1.390,P =8.23 × 10-6 ). Logistic regression identified that rs12101261 was an independent susceptibility locus of GD ( P=1.61 × 10-3 ).Furthermore,rs12101261 _T was strongly associated with GD ( OR =1.317,95％ CI 1.171-1.481,P=4.14× 10-4 ) in TRAb positive patients,but no association in TRAb negative patients ( OR=1.056,95％ CI 0.892-1.251,P=0.524 ).Serum TRAb concentration showed remarkable difference among three genotype groups of rs12101261.Conclusions Five SNPs in TSHR intron 1 are associated with GD.rs12101261 contributes to increased GD risk independently and is associated with serum TRAb level.
