The Role of Cytotoxic T-lymphocyte-associated Protein 4 (CTLA-4) Gene, Thyroid Stimulating Hormone Receptor (TSHR) Gene and Regulatory T-cells as Risk Factors for Relapse in Patients with Graves Disease
Abstract: graves’ disease (GD)
is the most common condition of thyrotoxicosis. The management of GD is initiated
with the administration of antithyroid drugs; however, it requires a long time
to achieve remission. In reality more than 50% of patients who had remission
may be at risk for relapse after the drug is stopped. This study aimed to
evaluate the role of clinical factors such as smoking habit, degree of
ophtalmopathy, degree of thyroid enlargement; genetic factors such as CTLA-4
gene on nucleotide 49 at codon 17 of exon 1, CTLA-4 gene of promotor -318, TSHR
gene polymorphism rs2268458 of intron 1; and immunological factors such as
regulatory T cells (Treg) and thyroid receptor antibody (TRAb); that affecting
the relapse of patients with Graves’ disease in Indonesia. Methods: this was a
case-control study, that compared 72 subjects who had relapse and 72 subjects
without relapse at 12 months after cessation of antithyroid treatment, who met
the inclusion criteria. Genetic polymorphism examination was performed using
PCR-RFLP. The number of regulatory T cells was counted using flow cytometry
analysis and ELISA was used to measure TRAb. The logistic regression was used
since the dependent variables were categorical variables. Results: the analysis
of this study demonstrated that there was a correlation between relapse of
disease and family factors (p=0.008), age at diagnosis (p=0.021), 2nd degree of
Graves’ ophthalmopathy (p=0.001), enlarged thyroid gland, which exceeded the
lateral edge of the sternocleidomastoid muscles (p=0.040), duration of
remission period (p=0.029), GG genotype of CTLA-4 gene on the nucleotide 49 at
codon 17 of exon 1 (p=0.016), CC genotype of TSHR gene on the rs2268458 of
intron 1 (p=0.003), the number of regulatory T cells (p=0.001) and TRAb levels
(p=0.002). Conclusion: genetic polymorphisms of CTLA-4 gene on the nucleotide
49 at codon 17 of exon 1, TSHR gene SNP rs2268458 of intron 1, number of
regulatory T cells and TRAb levels play a role as risk factors for relapse in
patients with Graves’ disease.
Keywords: graves’ disease;
relapse; CTLA-4 gene exon 1; CTLA-4 gene with promotor-318; TSHR gene rs2268458
intron 1; Regulatory T cells; Thyroid Receptor Antibody (TRAb)
Author: Fatimah Eliana,
Pradana Suwondo, Asmarinah Asmarinah, Alida Harahap, Samsuridjal Djauzi, Joedo
Prihartono, Tjokorda Gde Dalem Pemayun
Journal Code: jpkedokterangg170340
