低促甲状腺激素水平结节性甲状腺肿的发生发展与促甲状腺激素受体基因D727E多态性的相关性研究

Association of the occurrence and development of nodular goiter of low thyroid stimulating hormone levels with the D727 E polymorphism of the thyroid stimulating hormone receptor gene

目的通过检测促甲状腺激素受体(TSHR)基因727位密码子(p.Asp727Glu,p.D727E)多态性在结节性甲状腺肿(NG)中的分布,探讨其与低促甲状腺激素(TSH)水平NG发生发展的相关性。方法收集2018年1月至2019年12月上海交通大学医学院附属第一人民医院南院乳腺甲状腺外科收治的低TSH水平NG患者共17例设为低TSH组,另随机选取同期正常TSH水平的10例NG患者作为正常组。对27例患者组织切片提取DNA,进行TSHR基因全外显子测序。统计分析TSHR基因D727E多态性与临床病理特征的相关性。结果TSHR D727E GC+GG基因型在NG患者中占37.0%(10/27)。亚组分析显示,低TSH组NG患者GC+GG基因型的发生率明显高于正常组(52.9%vs 10.0%,P=0.042)。低TSH组中,GC+GG基因型较CC型年龄更大[(55.00±16.30)岁vs(40.38±14.09)岁,P=0.060]、最大径更小[(2.34±1.58)cm vs(3.97±2.13)cm,P=0.101],在正常组未见。在NG患者中,男性更易表现为GC+GG型(71.4%vs 25.0%,P=0.029)。结论低TSH水平NG的发生和发展可能与TSHR D727E GC+GG基因型相关。

Objective To test the distribution of thyroid stimulating hormone receptor(TSHR)gene 727 codon polymorphism(p.Asp727Glu,p.D727E)in nodular goiter(NG),and explore the occurrence and development of NG with low thyroid stimulating hormone(TSH)level.Methods A total of 17 cases of NG with low TSH level were collected as low TSH level group from January 2018 to December 2019 in the Department of Breast-Thyroid Surgery,South Campus of the First People’s Hospital Affiliated to Shanghai Jiao Tong University,and 10 cases of NG with normal TSH level were randomly selected as normal group.DNA was extracted from tissue sections of all 27 patients for whole exon sequencing of TSHR gene.The correlation between TSHR gene D727E polymorphism and clinical data was statistically analyzed.Results TSHR D727E GC+GG genotype accounted for 37.0%(10/27)of NG patients.Subgroup analysis showed that the incidence of GC+GG genotype in low TSH level group was significantly higher than that in normal group(52.9%vs 10.0%,P=0.042).In low TSH level group,GC+GG genotype had a tendency to be older[(55.00±16.30)years vs(40.38±14.09)years,P=0.060]and smaller lesions[(2.34±1.58)cm vs(3.97±2.13)cm,P=0.101],which was not seen in normal group.In NG patients,males were more likely to be GC+GG genotype(71.4%vs 25.0%,P=0.029).Conclusion The occurrence and development of NG with low TSH level may be associated with TSHR D727E GC+GG genotype.