TSHR第三胞内袢基因突变与毒性多结节性甲状腺肿发病的相关研究

Relationship between gene mutation in the third intracellular loop of thyrotropin receptor and pathogenesis of toxic multinodular goiter

目的探讨促甲状腺激素受体(TSHR)第三胞内袢基因突变在毒性多结节性甲状腺肿(TMG)自主高功能性形成中的作用。方法将16例TMG患者手术切除标本及其作为对照的甲状腺正常组织,用酚-氯仿-异戊醇法提取基因组DNA,对目的基因片断进行聚合酶链反应(PCR)及行DNA测序。结果在16例TMG 标本中,发现3例为622位密码子的点突变。异亮氨酸被苯丙氨酸置换(I622F,ATT→TTT),2例为单碱基插入性突变,在1928位和1929位核酸之间播入了一个鸟嘌呤核苷酸(G),使该密码子609位以后氨基酸发生了移码突变。在对照组中,未发现TSHR基因突变。结论 TSHR第三胞内袢基因突变,可能在TMG发病中起重要作用。

Objective To probe into the effects of gene mutation in the third Intracellular loop of thyrotropin receptor（TSHR） on the pathogenesis of autonomic and hyperfunctioning toxic multinodular goiter（TMG）. Methods TMG specimens were obtained from 16 cases diagnosed as TMG, with normal thyroid tissues adjacent to the tumors as controls. The genomic DNA was extracted with phenol-chlormethyl-isoamyl alcohol extraction and ethanol precipitation. The DNA fragments were amplified by PCR, and direct sequencing of the PCR products was performed. Results In sequence analysis, 3 TMG specimens of 16 cases displayed one point mutation at codon 620 （1622F, ATT→TIT）, and two cases of insertion mutations with guanine nucleotide （G） inserted between nucleotide 1 928 and 1 929 were identified. No mutations were found in the controls. Conclusion The gene mutations in the third intracellular looo of TSHR may be responsible for the Dathozenesis of TMG.