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.

Dorota Pastuszak-Lewandoska; Daria Domańska; Magdalena Rudzińska; Artur Bossowski; Anna Kucharska; Ewa Sewerynek; Karolina Czarnecka; Monika Migdalska-Sęk; Barbara Czarnocka

doi:10.18388/abp.2013_2034

Dorota Pastuszak-Lewandoska Department of Molecular Bases of Medicine, 1st Chair of Internal Diseases, Medical University of Lodz, Łódź, Poland.;
Daria Domańska Department of Molecular Bases of Medicine, 1st Chair of Internal Diseases, Medical University of Lodz, Łódź, Poland.;
Magdalena Rudzińska Department of Biochemistry & Molecular Biology, Medical Center of Postgraduate Education, Warsaw, Poland.;
Artur Bossowski Department of Pediatrics, Endocrinology, Diabetology with Cardiology Division, Medical University, Bialystok, Białystok, Poland.;
Anna Kucharska Department of Pediatrics and Endocrinology, Medical University of Warsaw, Warsaw, Poland.;
Ewa Sewerynek Department of Endocrine Disorders and Bone Metabolism, 1st Chair of Endocrinology, Medical University of Lodz, Łódź, Poland.;
Karolina Czarnecka Department of Molecular Bases of Medicine, 1st Chair of Internal Diseases, Medical University of Lodz, Łódź, Poland.;
Monika Migdalska-Sęk Department of Molecular Bases of Medicine, 1st Chair of Internal Diseases, Medical University of Lodz, Łódź, Poland.;
Barbara Czarnocka Department of Biochemistry & Molecular Biology, Medical Center of Postgraduate Education, Warsaw, Poland.;

DOI: https://doi.org/10.18388/abp.2013_2034

Abstract

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.