The objective of the current study is to explore the association of thyroid-stimulating hormone receptor (TSHR) rs1991517 polymorphism (c.2337 C > G, p.D727E) with congenital hypothyroidism (CH) through a case–control study followed by a meta-analysis. The case–control study was based on 45 CH subjects and 700 healthy controls. Meta-analysis comprised of seven published studies and our current findings (1044 CH cases and 1649 healthy controls). The allele contrast model showed that the presence of G- allele increased CH risk by 45% (OR: 1.45, 95% CI 1.20–1.76) and 41% (OR: 1.41, 95% CI 1.03–1.93) in fixed effect and random effect models, respectively. The GG- genotype is associated with 2.3-fold (95% CI 1.32–3.99) increased risk for CH in the fixed-effect model. I² (0.58) and Cochran’s Q test (Q: 16.72, p = 0.02) revealed evidence of heterogeneity in the association. No publication bias was observed by Egger’s test (p = 0.70). Sensitivity analysis revealed that even after excluding any study this polymorphism is associated with risk for CH. The rs1991517 mutation alters the binding affinity to cAMP (ΔG of 727D vs.727E: − 7.27 vs. − 7.34 kcal/mol). In conclusion, rs1991517 is a genetic risk factor for CH and exerts its impact by altering cAMP-mediated signal transduction.

本研究的目的是通过病例对照研究和荟萃分析，探讨促甲状腺激素受体 ( TSHR ) rs1991517 多态性 (c.2337 C > G，p.D727E) 与先天性甲状腺功能减退症 (CH) 的关系。 -分析。病例对照研究以 45 名 CH 受试者和 700 名健康对照为基础。荟萃分析包括七项已发表的研究和我们当前的研究结果（1044 名慢性肝炎病例和 1649 名健康对照）。等位基因对比模型显示，在固定效应和随机研究中，G 等位基因的存在使 CH 风险增加 45%（OR：1.45，95% CI 1.20–1.76）和 41%（OR：1.41，95% CI 1.03–1.93）分别为效应模型。在固定效应模型中，GG 基因型与 CH 风险增加 2.3 倍 (95% CI 1.32–3.99) 相关。 I ² (0.58) 和 Cochran's Q检验（ Q ：16.72， p = 0.02）揭示了相关性异质性的证据。 Egger 检验未发现发表偏倚 ( p = 0.70)。敏感性分析显示，即使排除任何研究，这种多态性也与 CH 风险相关。 rs1991517 突变改变了与 cAMP 的结合亲和力（727D 与 727E 的 ΔG：− 7.27 与 − 7.34 kcal/mol）。总之，rs1991517 是 CH 的遗传危险因素，并通过改变 cAMP 介导的信号转导发挥其影响。