INTERLEUKIN-4 (IL-4) AND INTERLEUKIN-4 RECEPTOR ALPHA CHAIN (IL-4Rα) GENE POLYMORPHISMS IN EGYPTIAN RHEUMATIC ARTHRITIS PATIENTS

Document Type : Original Article

Authors

1 Biochemistry Division, Dept. of Chemistry, Faculty of Science, Zagazig University

2 Faculty of Medicine, Zagazig University, Egypt

3 Faculty of Medicine, Zagazig University, Egypt.

Abstract

Rheumatoid arthritis (RA) is considered a Th1-driven disease. Interleukin 4 (IL-4) binds to its receptor, promoting Th2 differentiation and limiting Th1 responses, but its role in the pathogenesis of RA is conflicting. Objective: to evaluate the occurrence of variants of interleukin-4 (IL-4) and Interleukin-4 Receptor Alpha chain (IL-4 RA) gene in patients with rheumatoid arthritis and their possible contribution to disease severity. Methods: We analyzed 2 polymorphisms of the IL4 gene and 2 polymorphisms of IL-4 RA in patients with RA and in a control population, as well as measuring serum RF as a disease severity parameter. Results: The IL-4 –590 TT genotype (P<0.001) and The IL4 –590T allele (OR 2.84, 95% CI 1.0-8.77, p=0.03) were significantly more frequent in patients with RA than in controls, this is similar for IL-4 VNTR RP1⁄RP1 genotype (P<0.001) and IL-4 RP1 allele (OR 2.91 CI 0.92-10.23, P=0.04). Higher frequency of IL-4 RA I50V genotypes (P= 0.02) in RA patients compared with controls were also found. Nevertheless, the more severe form of RA is observed in patients carrying the IL-4 -590 T allele as compared with homozygous patients. The IL-4RA Q576 allele and IL-4RA V50 allele were significantly associated with the sever form of RA. Conclusion: The IL-4 -590 C/T, IL-4 VNTR in intron-3 and IL-4Rα I50V polymorphism were associated with RA susceptibility in Egyptian population. IL-4Rα I50V and IL-4Rα Q576R polymorphisms may be may be a genetic risk factor for RA severity.