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CTLA-4 polymorphisms (+49 A/G and -318 C/T) are important genetic determinants of AITD susceptibility and predisposition to high levels of thyroid autoantibodies in Polish children - preliminary study

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Pastuszak-Lewandoska D., Domańska D., Rudzińska M., Bossowski A., Kucharska A., Sewerynek E., Czarnecka K., Migdalska-Sęk M., Czarnocka B.
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2013
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vol. 60
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issue 4
641-646
EN
Autoimmune thyroid diseases (AITDs), including Hashimoto' s thyroiditis (HT) and Graves' disease (GD), are related to environmental and genetic factors. We analyzed the association of cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) gene two polymorphisms (+49 A/G, -318 C/T) with HT and GD development in Polish children, and correlated both polymorphisms with the production of thyroid autoantibodies (TPOAb and TgAb). The study involved 49 AITD patients (age 10-19) with HT (n=25) or GD (n=24) and 69 healthy controls. SNP genotyping was performed using genomic DNA and TaqMan® probes. The obtained results indicated that CTLA-4 +49 GG genotype was significantly more frequent in both HT and GD patients, whereas the AA genotype was more common in controls. CTLA-4-318 CT genotype was significantly more frequent in AITD, and the CC genotype more often occurred in controls. Significantly higher median TPOAb and TgAb values were associated with G allele in HT, and with T allele in GD patients. Concluding, both studied polymorphisms seem to be important genetic determinants of the risk of HT and GD, and appear to be associated with a predisposition to high levels of TAbs and clinical AITD. The obtained results give more information on the distribution of the CTLA-4 polymorphism in Polish AITD children, and further support the proposal that the CTLA-4 gene plays an important role in a TAb production.
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