Tumor Necrosis Factor-alpha (TNF-α) as a Therapeutic Target in Rheumatoid Arthritis (RA) Patients

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.