Kollati Yedukondalu, Akella Radha Rama Devi, Naushad Shaik Mohammad, Thalla Maunika, Reddy G Bhanuprakash, Dirisala Vijaya R
Department of Biotechnology, Vignan's University, Vadlamudi, Guntur, Andhra Pradesh 522213 India.
Department of Genetics, Rainbow Children's Hospital, Banjara Hills, Hyderabad, Telangana 500009 India.
3 Biotech. 2020 Jun;10(6):285. doi: 10.1007/s13205-020-02273-7. Epub 2020 Jun 1.
The objective of the current study is to explore the association of thyroid-stimulating hormone receptor () 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. (0.58) and Cochran's test (: 16.72, = 0.02) revealed evidence of heterogeneity in the association. No publication bias was observed by Egger's test ( = 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及荟萃分析，探讨促甲状腺激素受体（）rs1991517多态性（c.2337 C＞G，p.D727E）与先天性甲状腺功能减退症（CH）的关联。病例对照研究基于45例CH患者和700例健康对照。荟萃分析纳入了七项已发表的研究及我们当前的研究结果（1044例CH病例和1649例健康对照）。等位基因对比模型显示，在固定效应模型和随机效应模型中，G等位基因的存在分别使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）。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。（0.58）和 Cochr an检验（：16.72，=0.02）显示该关联存在异质性证据。通过Egger检验未观察到发表偏倚（=0.70）。敏感性分析表明，即使排除任何一项研究，该多态性仍与CH风险相关。rs1991517突变改变了对cAMP的结合亲和力（727D与727E的ΔG：-7.27与-7.34 kcal/mol）。总之，rs1991517是CH的一个遗传危险因素，通过改变cAMP介导的信号转导发挥作用。
