ASSOCIATION OF CTLA-4 AND PTPN-22 GENES POLYMORPHISMS WITH INCREASED RISK OF AUTOIMMUNE THYROIDITIS IN TATAR POPULATION

Abstract

The aspects of autoimmune thyroiditis (AIT) remain quite actual, since many issues of etiology, pathogenesis, morphology, classification, diagnostics, therapy and prediction of this disorder are far from final solution. Since disturbances of fine molecular immune mechanisms underlie pathogenesis of either immune disorder, the genes coding its main components, are regarded as potential candidate genes predisposing for AIT, e.g., genes of surface antigen (CTLA-4) and protein tyrosine phosphatase non-receptor 22 (PTPN-22). We have performed genotyping of 298 Tatar women in Tatar Republic (Russia) with respect to age and biochemical parameters (control group, 137 persons; AIT group, 161 patients). The following gene polymorphisms were tested: +49 А/G, -318 С/Т, -1661 А/G of СТLA-4 gene, and 1858 С/Т polymorphism of PTPN-22 gene. Genotyрing was performed by PCR-RFLP method as described earlier. The data were analyzed using Chi-square test and 95% confidential interval (CI). The frequencies of CTLA-4 -1661 G allele and genotype A/G and +49 G/A G allele and genotype GG carriers were significantly higher in AIT patients than in controls (P = 0.04, OR 1.84, 95% CI 2.31-1.4; P = 0.001, OR 2,0 95% CI 1.62-2.31 respectively), with increased contents of serum antibodies to thyroglobulin (OR, 1.56, 95% CI 2.25-3.6; OR 1.12, 95% CI 1.9-2.75, respectively) and to thyroperoxidase (OR 1.3, 95% CI 1.5-4.1 for G/G genotype of +49 A/G polymorphism), independently of age (р < 0,05). We showed that the combinations of A/G, T/C and G/G genotypes of -1661 A/G, -318 T/C and +49 G/A polymorphisms is associated with increased risk of genetic predisposition to ITD in Tatar women (OR 7.87, 95% CI 2.03-3.25). A strong association was also observed between the increased level of antibodies to TPO (> 1000 ME/l) and GG genotype of +49 G/A polymorphism (OR 1.3, 95% CI 1.5-4.1) and antibodies to TG (> 100 ME/l) and genotypes A/G and G/G of CTLA-4 -1661 A/G and +49 G/A polymorphisms (OR 1.56, 95% CI 2.25-3.6; OR 1.12, 95% CI 1.9-2.75, respectively), independently of age. The genotypes -318 T/C and 1858 T/C of CTLA-4 and PTPN-22 genes, respectively, are not associated with AITD in Tatar women (p > 0.05). Our results suggest that polymorphisms of CTLA-4 and PTPN-22 genes may modify individual susceptibility to autoimmune thyroiditis in Tatar women.

Keywords

• autoimmune thyroiditis
• protein tyrosine phosphatase
• сtla gene