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Volume 11
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10.3390/biomedicines11041155
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Article

NR3C1 rs6198 Variant May Be Involved in the Relationship of Graves’ Disease with Stressful Events

by
Matheus Nascimento
1,
Elisângela Souza Teixeira
1,
Izabela Fernanda Dal’ Bó
1,
Karina Colombera Peres
1,
Larissa Teodoro Rabi
1,2,3,
Adriano Namo Cury
4,5,
Natália Amaral Cançado
4,5,
Ana Beatriz Pinotti Pedro Miklos
6,
Fernando Schwengber
6,
Natássia Elena Bufalo
1,7,8 and
Laura Sterian Ward
1,*
1
Laboratory of Cancer Molecular Genetics, School of Medical Sciences, University of Campinas (UNICAMP), Campinas 13083-888, SP, Brazil
2
Department of Biomedicine, Nossa Senhora do Patrocínio University Center (CEUNSP), Itu 13300-200, SP, Brazil
3
Institute of Health Sciences, Paulista University (UNIP), Campinas 13043-900, SP, Brazil
4
Unit of Endocrinology and Metabolism, Santa Casa de Misericórdia de São Paulo, São Paulo 01221-010, SP, Brazil
5
Discipline of Endocrinology, School of Medical Sciences of Santa Casa de São Paulo (FCMSC-SP), Sao Paulo 01221-010, SP, Brazil
6
Endocrinology and Metabology Service of the Institute of Medical Assistance to State Civil Servants (IAMSPE), São Paulo 04029-000, SP, Brazil
7
Department of Medicine, Max Planck University Center, Indaiatuba 13343-060, SP, Brazil
8
Department of Medicine, São Leopoldo Mandic and Research Center, Campinas 13045-755, SP, Brazil
*
Author to whom correspondence should be addressed.
Biomedicines 2023, 11(4), 1155; https://doi.org/10.3390/biomedicines11041155
Submission received: 13 February 2023 / Revised: 28 March 2023 / Accepted: 10 April 2023 / Published: 12 April 2023
(This article belongs to the Section Endocrinology and Metabolism Research)
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Abstract

Although stressful events are known to trigger Graves’ disease (GD), the mechanisms involved in this process are not well understood. The NR3C1 gene, encoding for the glucocorticoid receptor (GR), presents single nucleotide polymorphisms (SNPs) that are associated with stress-related diseases. To investigate the relationship between NR3C1 SNPs, GD susceptibility, and clinical features, we studied 792 individuals, including 384 patients, among which 209 presented with Graves’ orbitopathy (GO), and 408 paired healthy controls. Stressful life events were evaluated in a subset of 59 patients and 66 controls using the IES-R self-report questionnaire. SNPs rs104893913, rs104893909, and rs104893911 appeared at low frequencies and presented similar profiles in patients and controls. However, variant forms of rs6198 were rarer in GD patients, suggesting a protective effect. Stressful events were more common in patients than controls, and were reported to have clearly occurred immediately before the onset of GD symptoms in 23 cases. However, no association was found between these events and rs6198 genotypes or GD/GO characteristics. We suggest that the NR3C1 rs6198 polymorphism may be an important protective factor against GD, but its relationship with stressful events needs further investigation.
Keywords: Graves’ disease; stress; psychological; pituitary–adrenal system; single nucleotide polymorphism Graves’ disease; stress; psychological; pituitary–adrenal system; single nucleotide polymorphism

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MDPI and ACS Style

Nascimento, M.; Teixeira, E.S.; Dal’ Bó, I.F.; Peres, K.C.; Rabi, L.T.; Cury, A.N.; Cançado, N.A.; Miklos, A.B.P.P.; Schwengber, F.; Bufalo, N.E.; et al. NR3C1 rs6198 Variant May Be Involved in the Relationship of Graves’ Disease with Stressful Events. Biomedicines 2023, 11, 1155. https://doi.org/10.3390/biomedicines11041155

AMA Style

Nascimento M, Teixeira ES, Dal’ Bó IF, Peres KC, Rabi LT, Cury AN, Cançado NA, Miklos ABPP, Schwengber F, Bufalo NE, et al. NR3C1 rs6198 Variant May Be Involved in the Relationship of Graves’ Disease with Stressful Events. Biomedicines. 2023; 11(4):1155. https://doi.org/10.3390/biomedicines11041155

Chicago/Turabian Style

Nascimento, Matheus, Elisângela Souza Teixeira, Izabela Fernanda Dal’ Bó, Karina Colombera Peres, Larissa Teodoro Rabi, Adriano Namo Cury, Natália Amaral Cançado, Ana Beatriz Pinotti Pedro Miklos, Fernando Schwengber, Natássia Elena Bufalo, and et al. 2023. "NR3C1 rs6198 Variant May Be Involved in the Relationship of Graves’ Disease with Stressful Events" Biomedicines 11, no. 4: 1155. https://doi.org/10.3390/biomedicines11041155

APA Style

Nascimento, M., Teixeira, E. S., Dal’ Bó, I. F., Peres, K. C., Rabi, L. T., Cury, A. N., Cançado, N. A., Miklos, A. B. P. P., Schwengber, F., Bufalo, N. E., & Ward, L. S. (2023). NR3C1 rs6198 Variant May Be Involved in the Relationship of Graves’ Disease with Stressful Events. Biomedicines, 11(4), 1155. https://doi.org/10.3390/biomedicines11041155

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