TSHR基因内含子1多态性与山东潍坊地区汉族人群Graves’眼病关系分析  

Association of TSHR gene intron 1 region polymorphism with Graves’ophthalmopathy in Han population from Weifang city in Shandong Province

作　　者：王靖文 柳林[2] 马晓婧 刘梦妍 高素敏 WANG Jingwen;LIU Lin;MA Xiaojing;LIU Mengyan;GAO Sumin(Department of Internal Medicine,Weifang Medical University,Weifang 261053,China;Department of Endocrinology,Weifang People's Hospital;Plastic Surgery Institute,Weifang Medical University)

机构地区：[1]潍坊医学院内科学教研室,山东潍坊261053 [2]潍坊市人民医院内分泌科 [3]潍坊医学院整形外科研究所

出　　处：《潍坊医学院学报》2021年第3期192-195,199,共5页Acta Academiae Medicinae Weifang

基　　金：山东省医药卫生发展计划项目(项目编号:2015WS0076);潍坊市科技发展计划项目(项目编号:2019YX004)。

摘　　要：目的探讨山东潍坊地区汉族人群促甲状腺激素受体(TSHR)基因内含子1区的核苷酸多态性位点(SNP)rs179247多态性与Graves’眼病(GO)的关系。方法收集2010年1月~2020年8月确诊的Graves’病(GD)患者278例,依据是否合并GO分为GO组与NGO组,收集患者相关临床数据(如发病年龄、甲状腺肿分级、家族史、吸烟史等);留取患者静脉血,提取样本DNA后进行聚合酶链反应(PCR),扩增产物用ABI3730XL基因测序仪进行一代基因测序;所有患者均用电化学发光法检测甲状腺功能指标(FT3、FT4、TSH、TPOAb、TRAb)、TSH受体抗体(TRAb)水平。结果 rs179247位点分型得到AA、AG、GG 3种基因型,两组间的等位基因、基因型之间差异无统计学意义(P值分别为0.432,0.698)。在男性患者中,吸烟是GO的危险因素之一(OR=8.038,95%CI=1.644-39.303,P=0.004);女性患者中,吸烟对GO的发生无影响(OR=1.571,95%CI=0.622-3.972,P=0.53)。两组间甲状腺肿分级的差异有统计学意义(P=0.03),GO组甲状腺肿分级明显高于NGO组;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rs179247与山东潍坊地区汉族人群Graves’眼病不存在关联;吸烟是男性GO患者的危险因素之一;GO患者甲状腺肿大程度较单纯Graves’病(GD)患者分级更高。Objective To investigate the association between polymorphisms of thyroid-stimulating hormone receptor(TSHR) gene intron 1(rs179247)and Graves’ ophthalmopathy(GO) in the China Han population from Weifang city, Shandong Province.Methods A total of 278 patients with Graves’ disease(GD) diagnosed from January 2010 to August 2020 were divided into GO group and NGO group according to whether they were complicated with GO or not.All clinical data of patients were collected, including the age of onset, diagnosis and treatment, living habits, smoking history, family history.The Venous blood of patients was collected.The DNA was extracted from the venous blood of the patients and amplified by PCR.The amplified products were sequenced and genotyped by ABI3730 XL genetic sequencing machines.Meanwhile, serum concentrations of thyroid hormone(FT3,FT4,TSH,TPOAb, TRAb)and TSH receptor antibodies(TRAb) were detected by electrochemiluminescence.Grading according to the degree of thyroid goiter and exophthalmos.The allele and genotype frequencies of rs179247 were calculated and Hardy-Weinberg equilibrium between SNPs was performed.Results Three genotypes of AA,AG and GG were obtained by rs179247,their proportions in group GO and group NGO were 10∶8∶1 and 16∶11∶1.According to statistical analysis: arrangement of alleles and genotypes of rs179247 did not differ in patients with and without GO(P=0.432;P=0.698).Smoking was a risk factor for GO in male GD patients(OR=8.038,95%CI=1.644-39.303,P=0.004);In female patients, smoking had no effect on GO(OR=1.571,95%CI=0.622-3.972,P=0.53).There was a significant difference of goiter grading between the two groups(P=0.03).The grade of goiter in GO Group was significantly higher than that in NGO group.Conclusion rsl79247 in TSHR intron 1 is not associated with GO in the China Han population from Weifang city, Shandong Province.Smoking is one of the risk factors in male patients with GO;the degree of goiter in patients with GO is higher than that in patients without GO.

关 键 词：Graves’眼病 自身免疫性甲状腺疾病 TSH受体抗体 多态性 单核苷酸 内含子 

分 类 号：R581[医药卫生—内分泌]