Abstract
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.
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Acknowledgements
The authors thank all the patients and healthy control in this study. The authors specially thank Dr. Pasumarthi NBS Srinivas, Uma Maheshwar P, Anusha Puvvada, Vignan’s University and National Institute of Nutrition for their support during the investigation.
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This study was partly supported by a grant from the Department of science and Technology-Science and Engineering Research Board (DST-SERB), Government of India (ECR/2016/00304).
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VRD, RRDA and SMN designed the work. The work was primarily executed by YK and MT under the supervision of VRD and SMN. RRDA and BRG gave constructive comments during the execution of the work. The manuscript was written by YK with extensive support of VRD and SMN. All the authors have given important insights and approved the final version of the manuscript.
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All procedures performed in studies involving human participants were in accordance with the ethical standards of the Institutional Ethics committee of Rainbow Hospital Institutional Ethics Committee (RCHBH/066/02-2018), Hyderabad, India and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.
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Informed written consents were obtained from parents and participants of all subjects included in the study.
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Kollati, Y., Akella, R.R.D., Naushad, S.M. et al. The rs1991517 polymorphism is a genetic risk factor for congenital hypothyroidism. 3 Biotech 10, 285 (2020). https://doi.org/10.1007/s13205-020-02273-7
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DOI: https://doi.org/10.1007/s13205-020-02273-7