IL1β exon5 3954 C/T Polymorphism: A potential Risk Factor for the Susceptibility to Rheumatoid Arthritis in Sudanese Patients

Abstract

Rheumatoid arthritis (RA) is a chronic inflammatory disease, usually causes progressive destruction of the joints. The genetic information is important for understanding the mechanisms of the disease. Cytokines are considered to play an important role in the pathogenesis of RA, as the imbalance between pro- and anti-inflammatory cytokines was known to promote the induction of autoimmunity, inflammation and joint destruction. This study aimed to demonstrate ―for the first time‖ a possible association of the 3954 C/T polymorphism (rs1143634) in exon 5 of IL-1β and the RA predisposition in Sudanese patients. A cross sectional association study was conducted, involving 84 unrelated RA patients and 93 healthy controls. The IL-1β (rs1143634) polymorphism was detected by PCR followed by RFLP technique using TaqI restriction enzyme. The result showed that 83.3% of the examined RA patients are females with high significant difference between cases and controls and five folds increased risk of female than males (P=0.001, OR=5.33, CI=2.64-10.77). 48.8% of the cases are at age less than 35 years. Family history of RA was reported in 26% of the cases, with no significant difference between cases and controls (p=0.07). None of the participants was smoker, 100% of the cases live sedentary live. The genotype analysis of IL1β exon5 3954 C/T (rs1143634) polymorphism showed a significant association with RA (P=0.001). In addition, the analysis considering the mutant genotypes CT+TT versus the wild genotype CC also suggests a high significant association of IL1β exon5 polymorphism with the risk of RA susceptibility in our patients and it increase peoples’ risk 2.6 folds to RA predisposition (P=0.001, OR=2.64, CI= 1.38-5.03). Carriage of the rare mutant IL-1 β (+3954) allele T was higher in arthritis patients as compared to the controls, however, the difference was insignificant (P=0.75). 68% of the RA patients showed articular manifestation, of which 70.6% have the mutant T allele. The result of this study, for the first time in Sudan, suggest that the 3954 C/T IL1 β (rs1143634) polymorphism is associated with the risk of RA, and the carriage of the mutant allele might be a predictive factor for the onset of clinical manifestation of rheumatoid arthritis in Sudanese patients.