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.
