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TSHR intronic polymorphisms (rs179247 and rs12885526) and their role in the susceptibility of the Brazilian population to Graves’ disease and Graves’ ophthalmopathy

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Abstract

Purpose

Intronic thyroid-stimulating hormone receptor polymorphisms have been associated with the risk for both Graves’ disease and Graves’ ophthalmopathy, but results have been inconsistent among different populations. We aimed to investigate the influence of thyroid-stimulating hormone receptor intronic polymorphisms in a large well-characterized population of GD patients.

Methods

We studied 279 Graves’ disease patients (231 females and 48 males, 39.80 ± 11.69 years old), including 144 with Graves’ ophthalmopathy, matched to 296 healthy control individuals. Thyroid-stimulating hormone receptor genotypes of rs179247 and rs12885526 were determined by Real Time PCR TaqMan® SNP Genotyping.

Results

A multivariate analysis showed that the inheritance of the thyroid-stimulating hormone receptor AA genotype for rs179247 increased the risk for Graves’ disease (OR = 2.821; 95 % CI 1.595–4.990; p = 0.0004), whereas the thyroid-stimulating hormone receptor GG genotype for rs12885526 increased the risk for Graves’ ophthalmopathy (OR = 2.940; 95 % CI 1.320–6.548; p = 0.0083). Individuals with Graves’ ophthalmopathy also presented lower mean thyrotropin receptor antibodies levels (96.3 ± 143.9 U/L) than individuals without Graves’ ophthalmopathy (98.3 ± 201.9 U/L). We did not find any association between the investigated polymorphisms and patients clinical features or outcome.

Conclusion

We demonstrate that thyroid-stimulating hormone receptor intronic polymorphisms are associated with the susceptibility to Graves’ disease and Graves’ ophthalmopathy in the Brazilian population, but do not appear to influence the disease course.

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Acknowledgments

The authors thank Espaço da Escrita—Coordenadoria Geral da Universidade—UNICAMP—for the language services provided. A special thanks to the team of statisticians, Cleide Aparecida Moreira Silva and our group from the Laboratory of Cancer Molecular Genetics (GEMOCA) of the School of Medical Sciences. This study received financial support from the Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP), Grant #2008/06567-5.

Conflict of interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Laboratory of Cancer Molecular Genetics, School of Medical Sciences (FCM), University of Campinas (UNICAMP), Rua Tessalia Vieira de Camargo, 126, Cidade Universitaria Zeferino Vaz, Campinas, SP, 13083-887, Brazil

    N. E. Bufalo, M. A. Marcello, R. P. Piai & L. S. Ward

  2. Division of Endocrinology, Pontifical Catholic University of Campinas (PUCCAMP), Av. John Boyd Dunlop, s/no Jardim Ipaussurama, Campinas, SP, 13060-904, Brazil

    R. B. dos Santos & J. H. Romaldini

  3. Department of Medical Genetics, University of Campinas (UNICAMP), Rua Tessalia Vieira de Camargo, 126, Cidade Universitaria Zeferino Vaz, Campinas, SP, 13083-887, Brazil

    R. Secolin

  4. HSPE-IAMSPE, Av. Ibirapuera, 981, Vila Clementino, São Paulo, 04029-000, Brazil

    J. H. Romaldini

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  1. N. E. Bufalo
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Bufalo, N.E., dos Santos, R.B., Marcello, M.A. et al. 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 38, 555–561 (2015). https://doi.org/10.1007/s40618-014-0228-9

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