Impact of single nucleotide polymorphisms of immune checkpoint CTLA-4 (SNP rs231775 and rs5742909) in susceptibility to Hashimoto's thyroiditis patients

Hashimoto thyroiditis (HT) is an autoimmune disorder causing thyroid cell destruction. This research aimed to evaluate CTLA-4 expression levels in patients with HT. As well as understand the risk and protective effects of two CTLA-4 SNPs polymorphisms (rs231775 and rs5742909) in Iraqi patients. A case control study was conducted on 50 HT patients (5 men and 45 females) which were assembled from Baghdad teaching hospital, Baghdad, Iraq. The relative gene expression method was used to measure the gene expression of CTLA-4 using qRT-PCR. The single nucleotide polymorphisms of (318C/T (rs231775) and +49A/G (rs5742909) were sequenced for data analysis. There was a significant increase of serum CTLA-4 levels and, there was a significant increase in fold change of CTLA-4 in HT patients compared to controls. The allele and genotype frequencies according to Hardy Weinberg equilibrium showed significant differences in HT patients in the study, the 318C/T (rs231775) variant showed differences in the AA genotype when compared to controls. However, there were no significant differences observed in the AG and GG genotypes. Similarly, for the CTLA-4 SNP +49A/G (rs5742909), no significant differences were found in the CC, CT, and TT genotypes. Despite these observations, both studied SNPs showed an increased expression of the soluble form and fold change of the immune checkpoint CTLA-4 in HT patients. The study reveals that CTLA-4 gene SNPs rs231775 and rs5742909 significantly influence the expression of CTLA-4 levels in HT patients, which potentially may cause HT incidence and development.