title: 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.
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.
authors.affiliation: Department of Molecular Bases of Medicine, 1st Chair of Internal Diseases, Medical University of Lodz, Łódź, Poland.
authors.forename: Dorota
authors.initials: D
authors.lastname: Pastuszak-Lewandoska
authors.affiliation: Department of Molecular Bases of Medicine, 1st Chair of Internal Diseases, Medical University of Lodz, Łódź, Poland.
authors.forename: Daria
authors.initials: D
authors.lastname: Domańska
authors.affiliation: Department of Biochemistry & Molecular Biology, Medical Center of Postgraduate Education, Warsaw, Poland.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Rudzińska
authors.affiliation: Department of Pediatrics, Endocrinology, Diabetology with Cardiology Division, Medical University, Bialystok, Białystok, Poland.
authors.forename: Artur
authors.initials: A
authors.lastname: Bossowski
authors.affiliation: Department of Pediatrics and Endocrinology, Medical University of Warsaw, Warsaw, Poland.
authors.forename: Anna
authors.initials: A
authors.lastname: Kucharska
authors.affiliation: Department of Endocrine Disorders and Bone Metabolism, 1st Chair of Endocrinology, Medical University of Lodz, Łódź, Poland.
authors.forename: Ewa
authors.initials: E
authors.lastname: Sewerynek
authors.affiliation: Department of Molecular Bases of Medicine, 1st Chair of Internal Diseases, Medical University of Lodz, Łódź, Poland.
authors.forename: Karolina
authors.initials: K
authors.lastname: Czarnecka
authors.affiliation: Department of Molecular Bases of Medicine, 1st Chair of Internal Diseases, Medical University of Lodz, Łódź, Poland.
authors.forename: Monika
authors.initials: M
authors.lastname: Migdalska-Sęk
authors.affiliation: Department of Biochemistry & Molecular Biology, Medical Center of Postgraduate Education, Warsaw, Poland.
authors.forename: Barbara
authors.initials: B
authors.lastname: Czarnocka
mesh_terms: D000293:Adolescent; D000483:Alleles; D001323:Autoantibodies / Q000235:genetics* / Q000276:immunology; D060908:CTLA-4 Antigen / Q000235:genetics*; D002648:Child; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006111:Graves Disease / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D050031:Hashimoto Disease / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D006801:Humans; D008297:Male; D020641:Polymorphism, Single Nucleotide; D013961:Thyroid Gland / Q000276:immunology / Q000473:pathology; D055815:Young Adult
chemical_list: D001323:Autoantibodies; D060908:CTLA-4 Antigen