Association of CTLA-4 gene polymorphism with Graves' disease and ophthalmopathy in Iranian patients.

Background: The cytotoxic T lymphocyte associated antigen-4 (CTLA-4) gene, is one of the candidate genes for susceptibility to Graves' disease. This study aimed to investigate the association of Graves' disease and Graves' ophthalmopathy with polymorphisms at position +49 in exon 1 and positions -318 and -1147 in the promoter region of CTLA-4 gene in Iranian patients.

Methods: A total of 205 unrelated Iranian patients with Graves' disease who were referred to the outpatient endocrine clinic of a large university general hospital and 103 sex-matched healthy controls were included in this study. Venous blood was obtained, genomic DNA was extracted by a salting out method, and the polymorphisms at positions +49, -318 and -1147 of the CTLA-4 gene were determined using the PCR-restriction fragment length polymorphism method (PCR-RFLP). Genotype and allele frequencies were determined.

Results: The frequency of the G allele at position +49 was significantly higher in patients with Graves' disease than in the control group (27.1% vs. 15.1%, OR=2.096, 95%CI=1.350-3.253 and p<0.01). Significant trends were not seen for the other two polymorphisms studied. In patients with ophthalmopathy, the frequency of the G allele at position +49 was higher than in those without ophthalmopathy (33.8% vs. 20.0%, OR=2.043, 95%CI=1.304-3.202 and p<0.01).

Conclusions: The results of this study suggest that the G allele at position +49 in exon1 of the CTLA-4 gene is associated with Graves' disease and Graves' ophthalmopathy in Iranian patients.