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  • Title: Tumor necrosis factor-α -308 polymorphism in North Indian rheumatoid arthritis patients and association with mRNA and serum TNF-α.
    Author: Jahid M, Rehan-Ul-Haq, Jha PK, Chawla D, Avasthi R, Ahmed RS.
    Journal: Clin Rheumatol; 2017 Oct; 36(10):2209-2216. PubMed ID: 28748515.
    Abstract:
    Rheumatoid arthritis (RA) is a severely disabling chronic autoimmune disorder that leads to progressive inflammation of the joints and surrounding tissues. TNF-α, a potent proinflammatory cytokine, plays a pivotal role in the pathogenesis of RA. The endogenous formation of TNF-α may be influenced by TNF-α promoter polymorphisms. Hence, the present study was designed to explore any possible association between genetic polymorphism of TNF-α -308 G/A, messenger RNA (mRNA) expression, serum levels of TNF-α, and inflammatory markers in North Indian RA patients. A total of 214 controls and 187 RA patients were recruited according to the revised American College of Rheumatology 2010 criteria. TNF-α -308 G/A genetic polymorphism within promoter region was analyzed by using PCR-RFLP. Levels of inflammatory markers and serum TNF-α were estimated by ELISA. The mRNA expression of TNF-α gene was measured by quantitative real-time PCR. Higher levels of autoantibodies (RF and anti-CCP) were present in RA patients as compared to controls. We found a positive and significant correlation of circulating TNF-α levels with RF (r = 0.18), anti-CCP (r = 0.16), and mRNA expression of TNF-α gene (r = 0.57) in RA patients. The mRNA expression levels of TNF-α was 4.5-fold higher in patients with RA as compared to controls. The heterozygous mutant variants (G/A) and homozygous mutant variants (A/A) were found to be significantly associated with RA as compared to control (OR = 1.52 and 3.02, respectively). Our observations illustrated a significant association of allele -308 A TNF-α with progression of RA. Significant and positive correlation of TNF-α levels with mRNA expression and inflammatory marker levels suggests that serum TNF-α may be a susceptibility marker for RA.
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