TSHR Gene (rs179247) Polymorphism and Susceptibility to Autoimmune Thyroid Disease: A Systematic Review and Meta-Analysis

Overview

Journal Endocrinol Metab (Seoul)

Specialty Endocrinology

Date 2024 Aug 1

PMID 39086275

Authors

Hendra Zufry

Timotius Ivan Hariyanto

Affiliations

Soon will be listed here.

Abstract

Backgruound: Both Graves' disease (GD) and Hashimoto's thyroiditis (HT) are classified as autoimmune thyroid diseases (AITDs). It has been hypothesized that changes in the thyroid-stimulating hormone receptor (TSHR) gene may contribute to the development of these conditions. This study aimed to analyze the correlation between the TSHR rs179247 gene polymorphism and susceptibility to AITD.

Methods: We conducted a thorough search of the Google Scholar, Scopus, Medline, and Cochrane Library databases up until March 2, 2024, utilizing a combination of relevant keywords. This review examines data on the association between TSHR rs179247 and susceptibility to AITD. Random-effect models were employed to assess the odds ratio (OR), and the findings are presented along with their respective 95% confidence intervals (CIs).

Results: The meta-analysis included 12 studies. All genetic models of the TSHR rs179247 gene polymorphism were associated with an increased risk of developing GD. Specifically, the associations were observed in the dominant model (OR, 1.65; P<0.00001), recessive model (OR, 1.65; P<0.00001), as well as for the AA genotype (OR, 2.09; P<0.00001), AG genotype (OR, 1.39; P<0.00001), and A allele (OR, 1.44; P<0.00001). Further regression analysis revealed that these associations were consistent regardless of the country of origin, sample size, age, and sex distribution. However, no association was found between TSHR rs179247 and the risk of HT across all genetic models.

Conclusion: This study suggests that the TSHR rs179247 gene polymorphism is associated with an increased risk of GD, but not with HT, and may therefore serve as a potential biomarker.

References

Ahmed R, Al-Shaikh S, Akhtar M . Hashimoto thyroiditis: a century later. Adv Anat Pathol. 2012; 19(3):181-6. DOI: 10.1097/PAP.0b013e3182534868. View

Pujol-Borrell R, Alvarez-Sierra D, Jaraquemada D, Marin-Sanchez A, Colobran R . Central Tolerance Mechanisms to TSHR in Graves' Disease: Contributions to Understand the Genetic Association. Horm Metab Res. 2018; 50(12):863-870. DOI: 10.1055/a-0755-7927. View

Kahaly G . Management of Graves Thyroidal and Extrathyroidal Disease: An Update. J Clin Endocrinol Metab. 2020; 105(12). PMC: 7543578. DOI: 10.1210/clinem/dgaa646. View

Dechairo B, Zabaneh D, Collins J, Brand O, Dawson G, Green A . Association of the TSHR gene with Graves' disease: the first disease specific locus. Eur J Hum Genet. 2005; 13(11):1223-30. DOI: 10.1038/sj.ejhg.5201485. View

Ploski R, Brand O, Jurecka-Lubieniecka B, Franaszczyk M, Kula D, Krajewski P . Thyroid stimulating hormone receptor (TSHR) intron 1 variants are major risk factors for Graves' disease in three European Caucasian cohorts. PLoS One. 2010; 5(11):e15512. PMC: 2991361. DOI: 10.1371/journal.pone.0015512. View

Liu L, Wu H, Wang Q, Zhu Y, Zhang W, Guan L . Association between thyroid stimulating hormone receptor gene intron polymorphisms and autoimmune thyroid disease in a Chinese Han population. Endocr J. 2012; 59(8):717-23. DOI: 10.1507/endocrj.ej12-0024. View

Rydzewska M, Goralczyk A, Goscik J, Wawrusiewicz-Kurylonek N, Bossowska A, Kretowski A . Analysis of chosen polymorphisms rs2476601 a/G - PTPN22, rs1990760 C/T - IFIH1, rs179247 a/G - TSHR in pathogenesis of autoimmune thyroid diseases in children. Autoimmunity. 2018; 51(4):183-190. DOI: 10.1080/08916934.2018.1486824. View

Sun W, Zhang X, Wu J, Zhao W, Zhao S, Li M . Correlation of TSHR and CTLA-4 Single Nucleotide Polymorphisms with Graves Disease. Int J Genomics. 2019; 2019:6982623. PMC: 6745126. DOI: 10.1155/2019/6982623. View

Antonelli A, Ferrari S, Corrado A, Di Domenicantonio A, Fallahi P . Autoimmune thyroid disorders. Autoimmun Rev. 2014; 14(2):174-80. DOI: 10.1016/j.autrev.2014.10.016. View

10.

Marin-Sanchez A, Alvarez-Sierra D, Gonzalez O, Lucas-Martin A, Selles-Sanchez A, Rudilla F . Regulation of Expression in the Thyroid and Thymus May Contribute to TSHR Tolerance Failure in Graves' Disease Patients via Two Distinct Mechanisms. Front Immunol. 2019; 10:1695. PMC: 6657650. DOI: 10.3389/fimmu.2019.01695. View

11.

Okosieme O, Taylor P, Evans C, Thayer D, Chai A, Khan I . Primary therapy of Graves' disease and cardiovascular morbidity and mortality: a linked-record cohort study. Lancet Diabetes Endocrinol. 2019; 7(4):278-287. DOI: 10.1016/S2213-8587(19)30059-2. View

12.

Bufalo N, Dos Santos R, Marcello M, Piai R, Secolin R, Romaldini J . TSHR intronic polymorphisms (rs179247 and rs12885526) and their role in the susceptibility of the Brazilian population to Graves' disease and Graves' ophthalmopathy. J Endocrinol Invest. 2014; 38(5):555-61. DOI: 10.1007/s40618-014-0228-9. View

13.

Inoue N, Watanabe M, Katsumata Y, Hidaka Y, Iwatani Y . Different genotypes of a functional polymorphism of the TSHR gene are associated with the development and severity of Graves' and Hashimoto's diseases. Tissue Antigens. 2013; 82(4):288-90. DOI: 10.1111/tan.12190. View

14.

Colobran R, Armengol M, Faner R, Gartner M, Tykocinski L, Lucas A . Association of an SNP with intrathymic transcription of TSHR and Graves' disease: a role for defective thymic tolerance. Hum Mol Genet. 2011; 20(17):3415-23. DOI: 10.1093/hmg/ddr247. View

15.

Brent G . Environmental exposures and autoimmune thyroid disease. Thyroid. 2010; 20(7):755-61. PMC: 2935336. DOI: 10.1089/thy.2010.1636. View

16.

Higgins J, Thompson S, Deeks J, Altman D . Measuring inconsistency in meta-analyses. BMJ. 2003; 327(7414):557-60. PMC: 192859. DOI: 10.1136/bmj.327.7414.557. View

17.

Xiong H, Wu M, Yi H, Wang X, Wang Q, Nadirshina S . Genetic associations of the thyroid stimulating hormone receptor gene with Graves diseases and Graves ophthalmopathy: A meta-analysis. Sci Rep. 2016; 6:30356. PMC: 4960547. DOI: 10.1038/srep30356. View

18.

Thornton A, Lee P . Publication bias in meta-analysis: its causes and consequences. J Clin Epidemiol. 2000; 53(2):207-16. DOI: 10.1016/s0895-4356(99)00161-4. View

19.

Stang A . Critical evaluation of the Newcastle-Ottawa scale for the assessment of the quality of nonrandomized studies in meta-analyses. Eur J Epidemiol. 2010; 25(9):603-5. DOI: 10.1007/s10654-010-9491-z. View

20.

Page M, McKenzie J, Bossuyt P, Boutron I, Hoffmann T, Mulrow C . The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ. 2021; 372:n71. PMC: 8005924. DOI: 10.1136/bmj.n71. View