Association of CTLA4 (rs4553808) and PTPN22 (rs2476601) gene polymorphisms with Hashimoto's thyroiditis disease: A case-control study and an In-silico analysis

In addition to other factors regarding the disease susceptibility, genetic factors are the main causes of Hashimoto's thyroiditis (HT) disease. CTLA4 and PTPN22 are the most prominent genes involved in the immune system regulation, thus effective in the pathogenesis of autoimmune diseases. In the current study, the association of two polymorphisms of CTLA4 and PTPN22 genes, 1661A/G (CTLA-4 gene) and C1858T (PTPN22 gene), with HT was investigated by PCR-RFLP (Polymerase Chain Reaction-Restriction Fragment Length Polymorphism) technique. The effects of -1661A/G and C1858T polymorphisms on the mRNA and protein structures of CTLA-4 and PTPN22 were investigated by an in silico analysis. There was no significant difference between the genotype and allele frequencies of PTPN-22 gene polymorphism (rs2476601) in case and control groups. There was a positive association between the frequency of heterozygous genotype of CTLA4-1661A/G polymorphism (rs4553808) and HT (P = .04), but no association was seen regarding allele frequencies. In-silico analysis predicted that the transition of allele A to allele G would lead to the loss of some of the binding sites. Also, the structural analysis of C1858T transition effect on protein revealed a significant influence on PTPN-22 function. Our results showed that heterozygous genotype of -1661A/G CTLA4 gene variation might be related with the risk of HT. •Association of heterozygous genotype of CTLA4-1661A/G polymorphism (rs4553808) and HT risk•No correlation between PTPN-22 gene polymorphism (rs2476601) and HT risk•The significant effect of C1858T transition (rs2476601) on PTPN-22 protein function