Endocrine Abstracts

The aim: Of this study was to investigate the association between two common CTLA-4 gene SNPs (49A/G in exon 1 and CT60 A/G in 3’UTR) and Graves’ disease outcome in Lithuanian population.

Methods: This case-control study was performed in the Hospital of Lithuanian University of Health Sciences. Graves’ disease patients (n=105) were divided into remission and failed treatment groups according to the final outcome of the disease. The remission group (n=49) – patients with euthyroid status minimum 1 year after antithyroid drugs (ATD) withdrawal. The failed treatment group (n=56) – patients submitted radioiodine therapy or surgery due to poor response to ATD therapy. Genomic DNA was extracted from the peripheral blood leukocytes with kit Qiagen GmbH, Hilden, Germany.

Results: The patients in failed treatment group had significantly higher frequency of GG genotype and a lower frequency of AA genotype than patients in remission group. Patients with GG homozygous genotype had more than four-fold (OR 4.94, 95% CI 1.38–17.65) and more than sixteen-fold (OR 16.91, 95% CI 1.83–156.62) increase in risk of ATD treatment failure compared to patients with homozygous genotype AA for 49A/G SNP and for CT60 SNP, respectively. When association of 49A/G and CT60 genotypes on the outcome of Graves’ disease was analyzed separately it provided significant prognostic information but after multiple logistic regression analysis these genetic markers were not independent of other factors. Only TRAb levels before treatment was independently associated with elevated odds of failure (OR 1.05, 95% CI 1.02–1.08).

Conclusion: the data shows significant association of two polymorphisms (A/G at position 49 and CT60 in 3’UTR) in the CTLA-4 gene with Graves’ disease in Lithuania and suggest that these genetic markers may provide important information in predicting high risk patients for failure to ATD therapy.