The rs1991517 polymorphism is a genetic risk factor for congenital hypothyroidism

• Published in: 3 Biotech 2020-06, Vol.10 (6), p.285-285, Article 285
• Main Authors: Kollati, Yedukondalu, Akella, Radha Rama Devi, Naushad, Shaik Mohammad, Thalla, Maunika, Reddy, G Bhanuprakash, Dirisala, Vijaya R.
• Format: Article
• Language: English
• Subjects: Agriculture; Alleles; Bioinformatics; Biomaterials; Biotechnology; Cancer Research; Chemistry; Chemistry and Materials Science; Congenital diseases; Cyclic AMP; Gene polymorphism; Heterogeneity; Hypothyroidism; Meta-analysis; Mutation; Original; Original Article; Polymorphism; Risk analysis; Risk factors; Sensitivity analysis; Signal transduction; Stem Cells; Thyroid; Thyroid-stimulating hormone; Thyroid-stimulating hormone receptors
• ISSN: 2190-572X; 2190-5738
• DOI: 10.1007/s13205-020-02273-7

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. I 2 (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.