IL-1B Gene Polymorphism and Susceptinility to Rheumatoid Arthritis in Ethnic Saudi Patients

IL-1 is an inflammatory cytokine that has been widely implicated in Rheumatoid Arthritis (RA). In Saudi Arabia, limited work has addressed the genetic bases of RA. In this case-control study, association of single nucleotide polymorphisms (SNPs) in the IL-1 gene is investigated in a well characterized Saudi cohort. Keeping in view the genetic heterogeneity of Saudi population, blood samples from 100 ethnic Saudi RA patients and 200 matched healthy controls were analyzed. Genotyping for SNPs including IL-1A +4845, IL-1B -511, IL-1B +3954 and IL-1RA +2018 was performed by amplifying the polymorphic region using PCR followed by restriction enzyme analysis on polyacrylamide gel electrophoresis (PAGE). Comparison of RA patient data and healthy controls revealed significant increase in the carriage rate of rare (2/2) genotype for IL-1B +3954 in the RA cases (13% in RA vs 5% in controls, P= 0.022). Subsequently the rare allele frequency (+3954T) was significantly increased in the RA patient group (frequency= 32.5% in RA patients P= 0.01) compared to controls (frequency= 22.5%). No differences were observed for the remaining polymorphisms, indicating that the rare allele of IL-1B +3954 is associated with susceptibility to RA in ethnic Saudis. Due to known extracellular pro-inflammatory activity of secretory IL-1B, it is suggested that this bi-allelic polymorphism could be used as a prognostic marker for RA in ethnic Saudis.