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Aim: To assess the probable role of +49AG polymorphism in susceptibility to SLE in an Egyptian population., Background: Systemic lupus erythematosus (SLE) is a compound inflammatory chronic disease distinguished through the release of autoantibodies. Cytotoxic T lymphocyte associated antigen-4 is a main down controller of T-cell response; its dysregulation could affect SLE pathogenesis by altered T cells activation to self-antigens., Objectives: To evaluate the CTLA-4 +49AG allelic and genotype frequency in a sample of the Egyptian population and correlate them with disease susceptibility and clinical severity., Materials and Methods: Including 100 patients with SLE and 100 healthy controls (age and gender matched), CTLA-4 exon 1 49 A>G Genotyping was done using Real-Time PCR., Results: No difference was noticed in genotype or allele distributions of the studied polymorphism between both groups. Similar genotypes and allele frequencies were established for the 2 groups after their stratification by the age of disease onset, clinical course, or severity., Conclusion: CTLA-4 +49AG gene polymorphism is not linked with the liability to develop SLE in the studied Egyptian population. Yet it is significantly related to disease severity., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)