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Thyroid autoantibody production is influenced by exon 1 and promoter CTLA-4 polymorphisms in patients with Hashimoto's thyroiditis
Zaletel, Katja ...
Strong genetic susceptibility to thyroid autoantibody (TAb) diathesis has beenshown and one of the major genes involved is probably CTLA-4 gene. Our recent study of patients with Graves' disease has ...demonstrated that exon 1 CTLA-4 gene polymorphism influences higher TAb production. Here, we evaluated the influence of exon 1 and promoter CTLA-4 polymorphisms on TAb production in109 newly diagnosed patients with Hashimoto's thyroiditis (HT). Serum TSH, thyroid peroxidase antibodies (TPOAb) and thyroglobulin antibodies (TgAb) weremeasured. 49 A/G and -318 C/T polymorphisms were detected using polyrnerase chain reaction amplifica- tion of genomic DNA and restriction fragment length poly- morphism analysis. Patients with AG and GG genotype had significantly higher TPOAb median values compared to patients with AA genoty pe (P < 0.003). Similarly, TgAb median value was significantly higher in AG patients and in the entire G-allele carrying group (P < 0.02). Compared to both T-allele carrying genotypes, CC genotype presented with significantly higher TPOAb median value (P < 0.02), whereas TgAb median values did not differ significantly between various genotypes. In conclusion, our results indicate that G allele influences higher TPOAb and TgAb production, whereas C allele affects especially TPOAb production in patients with HT. Therefore, ourfindings provide further evidence that CTLA-4 is a major TAb susceptibilitygene.
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