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Cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) is an inhibitory molecule that has an essential role in T-cell homeostasis and self-tolerance because of its inhibitory signals. Genetic polymorphisms in the CTLA-4 gene have been associated with several autoimmune diseases. We aimed to assess the association between the CTLA-4 +49 A/G polymorphism (rs231775) and rheumatoid arthritis (RA) in Egyptian RA patients. The study included 104 RA patients and 81 apparently healthy control individuals. The polymorphism was assessed using restriction fragment-length polymorphism analysis. Genotype distribution was compared between patients and controls under different models of inheritance. Under the codominant model, RA patients showed a higher frequency of AG and GG genotypes compared to the control subjects (p=0.0092). Under the dominant model, RA patients showed a higher frequency of AG and GG genotypes grouped together compared to control subjects (p=0.0026). Under the over-dominant model, the AG genotype was more frequent in RA patients compared to control subjects (p= 0.0395). No association was observed between CTLA-4 polymorphism rs231775 and RA using the recessive model (p=0.1356). A significant association was observed between carrying the G allele and the presence of RA (p=0.0032). In conclusion, our findings showed a positive association between the CTLA-4 gene +49 A>G polymorphism and RA. However, discrepancies in literature reflect both ethnic variability in CTLA-4 gene polymorphisms as well as the complex pathogenesis of RA.

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