ASSOCIATION OF CTLA-4 AND PTPN-22 GENE POLYMORPHISMS WITH THE DEVELOPMENT OF HYPOTHYROIDISM IN RUSSIAN PREGNANT WOMEN

Objective. To study an association of polymorphisms in the immunoregulatory genes of cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and protein tyrosine phosphatase, nonreceptor 22 (PTPN-22) with hypothyroidism in Russian pregnant women. Subject and methods. The investigation included 179 women with single pregnancy who were divided into 2 groups: 1) 66 with subclinical or overt hypothyroidism (a study group) and 2) 113 without severe extragenital disease, endocrinopathy, obstetric and gynecological complications (a control group). Hypothyroidism was diagnosed on the basis of measurement of thyroid-stimulating hormone levels (more than 2.5 IU/l) at the end of the first trimester to the beginning of the second trimester (10-16 weeks). The polymorphisms of the CTLA-4 (A49G) and PTPN-22 (C1858T) were determined by allele-specific polymerase chain reaction (PCR) using a fluorescence-labelled oligonucleotide probe and melting curve analysis. Results. Examinations of the levels of thyroid tissue antibodies revealed the latter to thyroid peroxidase and thyroglobulin more frequently in the study group (in 73.9 and 75.4%, respectively) than in the control one (in 8.9 and 9.7%, respectively), which suggested the probable autoimmune pattern of the disease. Genotyping in the examined groups indicated that pregnant women with CTLA-4 GG or GA genotype were more often identified in the study group than in the control one. On the contrary, AA genotype carriage was associated with the lower risk of hypothyroidism in the pregnant women (OR = 0.3; 95% CI, 0.12-0.68). At the same time, the examined groups were similar in the rate of PTPN22 C1858Tpolymorphism. Conclusion. The investigations demonstrated that the pregnant women may develop autoimmune hypothyroidism due to the G allele of the A49G CTLA-4 polymorphism.

CTLA4, PTPN22, hypothyroidism, autoimmunity, CTLA1, PTPN22, polymorphism