Pastuszak-Lewandoska Dorota, Domańska Daria, Rudzińska Magdalena, Bossowski Artur, Kucharska Anna, Sewerynek Ewa, Czarnecka Karolina, Migdalska-Sęk Monika, Czarnocka Barbara
Department of Molecular Bases of Medicine, 1st Chair of Internal Diseases, Medical University of Lodz, Łódź, Poland.
Department of Biochemistry & Molecular Biology, Medical Center of Postgraduate Education, Warsaw, Poland.
Acta Biochim Pol. 2013;60(4):641-6. Epub 2013 Dec 20.
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.
自身免疫性甲状腺疾病（AITD），包括桥本甲状腺炎（HT）和格雷夫斯病（GD），与环境和遗传因素有关。我们分析了细胞毒性T淋巴细胞相关抗原4（CTLA-4）基因的两个多态性位点（+49 A/G、-318 C/T）与波兰儿童HT和GD发病的关联，并将这两个多态性位点与甲状腺自身抗体（TPOAb和TgAb）的产生进行了相关性分析。该研究纳入了49例年龄在10至19岁之间的AITD患者，其中25例为HT患者，24例为GD患者，以及69例健康对照。使用基因组DNA和TaqMan®探针进行单核苷酸多态性（SNP）基因分型。所得结果表明，CTLA-4 +49 GG基因型在HT和GD患者中显著更常见，而AA基因型在对照中更常见。CTLA-4 -318 CT基因型在AITD患者中显著更常见，CC基因型在对照中更常出现。HT患者中，TPOAb和TgAb的中位数显著更高与G等位基因相关，而GD患者中与T等位基因相关。总之，所研究的两个多态性位点似乎都是HT和GD发病风险的重要遗传决定因素，并且似乎与高滴度甲状腺自身抗体（TAbs）及临床AITD的易感性相关。所得结果提供了更多关于波兰AITD儿童中CTLA-4多态性分布的信息，并进一步支持了CTLA-4基因在TAbs产生中起重要作用的观点。
