Association Study of Interleukin-15 (IL-15) Gene Polymorphisms in Rheumatoid Arthritis (RA)

Abstract

Rheumatoid arthritis is a chronic inflammatory disorder with a worldwide distribution involving all racial and ethnic groups. The incidence and prevalence of rheumatoid arthritis varies across different geographic regions of the world and across different time periods. It affects 0.5-1.0 per cent of the general population worldwide. In Pakistan it affects 0.1-0.2 per cent of the population. The disease can cause inflammation of one or more joints of the body. A number of cytokines regulate key inflammatory pathways that are involved in the progression of the disease. Interleukin-15 is one of the key cytokines in the pathogenesis of rheumatoid arthritis, which is secreted by synovial macrophages and is involved in the recruitment of inflammatory cells in the synovium, differentiation of osteoclast progenitors into preosteoclasts and regulation of the levels of other immunoregulatory molecule. The genetic polymorphisms, located in the regulatory regions of interleukin-15 gene might play a role in rheumatoid arthritis. The important role being played by interleukin-15 signifies the candidacy of this gene for disease pathogenesis. In this study, the association of two SNPs rs4956403 (SNP-1) and rs3806798 (SNP-2) located in the 5’ UTR region of interleukin-15 gene was studied in 40 rheumatoid arthritis patients from Pakistani population. Allele specific PCR was employed for the analysis of these polymorphisms and the results were analyzed statistically for any significant association of these polymorphisms with rheumatoid arthritis. The results of our study showed that SNP-1 and SNP-2 in interleukin-15 gene are not associated with rheumatoid arthritis in our patients. However, more molecules implicated in the inflammatory pathway of rheumatoid arthritis need to be investigated for the genetic association with disease pathogenesis and other single nucleotide polymorphisms (SNPs) located in the regulatory and untranslated regions of inteleukin-15 gene may have significant association towards rheumatoid arthritis, for which large scale data is required.