Background: Rhuematoid Arthritis influences all aspects of life as it causes co-morbiditis in vascular,metabolic and articular aspects.There are many factors that contribute to development of RA as genetic and environmental factors. Objectives: to evaluate the association between single nucleotide polymorphism of AIRE gene (SNP rs2075876) and risk of RA in Egyptian patients.Methods: Acase control study conducted on 50 participants collected:30 previously diagnosed rheumatoid arthritis according to ACR/EULAR critria (25 females and 5 males) and 20 healthy group age and sex matched controls. Participants were screened for routine laboratory investigations & immunological investigation as RF and anti-ccp and AIRE gene polymorphism by using real time polymerase chain reaction. On comparing the 2 groups (controls and cases) Results: the results showed that there is statistically significant difference between cases and controls regarding SNP rs2075876 for the distribution of genotype and alleles. Therefore,we conclude that there is strong association between AIRE gene SNP rs2075876 and risk of rheumatoid arthritis.