The study of CTLA-4 gene rs5742909 Polymorphism with Graves’ Ophthalmopathy

Abstract

Background: Graves’ disease is an autoimmune disease characterized by hyperthyroidism. In Graves’ hyperthyroidism, TSHR autoantibodies increase thyroid hormone activity. Individuals with Graves’ hyperthyroidism develop Graves’ ophthalmopathy through the action of autoantibodies and TSHR-specific T cells on TSHR receptors in orbital fibroblasts and adipocytesf. A measure of the immunity of the immune system to its own cells depends on the balance of their activating and inhibitory proteins. CTLA-4 protein is expressed on the surface of activated T lymphocytes and plays a role in hemostasis and negative regulation of immunity. CTLA-4 binds to the CD80/86 molecule on antigen-presenting cells and exerts an inhibitory effect. Therefore, the rs5742909 polymorphism, which is one of the factors that regulate the expression and activation of CTLA-4, may affect the immune balance, resulting in loss of response control and the development of autoimmune diseases. Aim: To compare allele and genotype frequency of CTLA-4 gene rs5247909 polymorphism in study groups. Materials and Methods: A total of 180 unrelated GD and GO patients, and 101 people in the control group participated in the study. Genomic DNA was extracted from participants from peripheral blood and alleles and genotypes were determined by real time PCR and allele-specific PCR. STATA 13.0 software was used for statistical processing of the results. Odds ratios (OR) were calculated by Binary Logistic Regression analysis. Results: The -319T allele of the rs5742909 SNP increasing the risk of Graves’ ophthalmopathy by 3.95 (95% CI, 2.097.48; p<0.001 times compared with controls. C/T (OR=4.94; 95% CI, 2.26-10.76; p<0.001) genotype were significantly more frequent in the group with Graves’ ophthalmopathy. Moreover, compared to the group with Graves’ disease the frequency of C/T (OR=4.43; 95% CI, 2.15-9.13; p=0.001) genotype was significantly higher among Graves’ ophthalmopathy patients. Conclusion: CTLA-4 gene rs5742909 polymorphism T allele and C/T genotype had a relatively high frequency and a strong risk effect in the group with Graves’ ophthalmopathy, indicating that this polymorphism may be a useful genetic marker for the differential diagnosis of Graves’ ophthalmopathy.