Abstract:
Rheumatoid Arthritis is a common systemic autoimmune disease. The disease prevalence
varies across different geographic regions of the world, affecting about 0.5-1.0 percent of
the general population worldwide. Where, in Pakistan about 0.1-0.2 percent people get
affected by RA. Chemokines and cytokines play a fundamental role in manipulating
inflammatory pathways, intricate in disease progression. Tumor Necrosis Factor-α is an
inflammatory cytokine, has an imperative foremost role in rheumatoid synovitis. Single
nucleotide polymorphisms in the regulatory region might play a significant role in disease
development, pathogenesis and gene expression. In this presented work, the association
analysis of rs1800630, rs1799724 and rs1800629 was studied in 268 individuals,
employing Allele specific PCR. Results were statistically assessed for any significant
association of these single nucleotide polymorphisms with RA. To ascertain association
with elevated serum Tumor Necrosis Factor alpha levels, enzyme-linked immune sorbent
assay was performed. No momentous difference was observed in our case-control study.
Moreover, efficacy of natural products (Sesame oil and Aloe vera) was investigated invitro
to determine the potent therapeutic compound against our protein. Sesame oil was
found to be more potent natural product decreasing tumor necrosis factor-α level.
Furthermore, world drug database was also screened using in-silico approaches. Four
structurally diverse novel hits were identified through our designed pharmacophore
model.
