49A/G and CT60 polymorphisms of the cytotoxic T-lymphocyte-associated antigen 4 gene associated with autoimmune thyroid disease

Ajda Bicek, Katja Zaletel, Simona Gaberscek, Edvard Pirnat, Blaz Krhin, Tanja Gmeiner Stopar, Sergej Hojker
Human Immunology 2009, 70 (10): 820-4
Single nucleotide polymorphisms in the CTLA-4 gene have been suggested as genetic factors in the susceptibility to autoimmune thyroid disease (AITD). In our case-control study, patients with Graves' disease, Hashimoto's thyroiditis, and postpartum thyroiditis and control subjects have been genotyped for two A/G single nucleotide polymorphisms (49A/G and CT60) of the CTLA-4 gene. The 49A/G polymorphism was genotyped by polymerase chain reaction-restriction fragment length polymorphism method using the enzyme BseXI and the CT60 polymorphism by real-time polymerase chain reaction. Results were analyzed by chi(2) test and linkage disequilibrium analysis. In a comparison of frequencies of GG genotype, a significant association of 49A/G and CT60 polymorphism existed only for Graves' disease. In the 49A/G polymorphism, the frequency of GG genotype was significantly higher (p = 0.0408) compared with controls; the frequency of the CT60 polymorphism was significantly higher as well (p = 0.0213). The frequencies of AA and AG genotypes in control subjects did not significantly differ from frequencies in AITD patients for both polymorphisms. Our results may therefore lend support to the hypothesis that humoral autoimmunity is correlated with 49A/G and CT60 polymorphisms of the CTLA-4 gene.

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