Association between CTLA-4 gene polymorphisms and Type 1 diabetes in Kurdish patients

Abstract

Type 1 diabetes (T1D) is an increasingly complex disease influenced by both genetic and environmental triggers, leading to overactivity of the immune system. This preliminary study was conducted to investigate the association of two common cytotoxic T lymphocyte antigen-4 (CTLA-4) variants with T1D susceptibility in the Kurdish population of Iraq. Additionally, we evaluated the correlation between these polymorphisms and anti-GAD antibody positivity, as well as their possible influence on CTLA-4 gene expression. In this study, 52 patients (28 males and 24 females) with T1D and 21 healthy control subjects were genotyped for two (CTLA-4) SNPs, A>G (rs231775) and -318 C>T (rs5742909), using direct DNA sequencing. Furthermore, serum anti-GAD antibody levels were measured by ELISA technique, and the expression of CTLA-4 levels was assessed with quantitative real-time PCR. We discovered that the A>G (rs231775) variant was significantly associated with T1DM. The G allele frequency was significantly higher in type 1 diabetes patients (36.5%, P = 0.0188). The -318 C/T polymorphism showed no significant differences between groups. The GG genotype of the +49A/G polymorphism exhibited a greater prevalence in anti-GAD positive patients relative to negative individuals (77.78% vs. 22.22%), indicating an elevated risk trend (OR = 2.77, 95% CI: 0.51–14.91); however, this finding did not achieve statistical significance (P = 0.28). The (CTLA-4) mRNA gene expression was observed to be non-significantly elevated in T1D relative to the control group (p = 0.1239). Our data indicate that the G allele of the CTLA-4 + 49 A>G variant is associated with increased T1D susceptibility in the Kurdish population, while the genotypic association showed a nominal trend.