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Tumor necrosis factor-α -308 polymorphism in North Indian rheumatoid arthritis patients and association with mRNA and serum TNF-α

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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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Acknowledgements

One of the authors Mohd Jahid is thankful to the Indian Council of Medical Research (ICMR) New Delhi for providing the Senior Research Fellowship (SRF).

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Authors and Affiliations

  1. Department of Biochemistry, University College of Medical Sciences and GTB Hospital (University of Delhi), Dilshad Garden, Delhi, 110095, India

    Mohd Jahid, Puja Kumari Jha & Rafat Sultana Ahmed

  2. Department of Orthopedics, University College of Medical Sciences and GTB Hospital (University of Delhi), Dilshad Garden, Delhi, 110095, India

    Rehan-Ul-Haq

  3. Central Research Laboratory, University College of Medical Sciences and GTB Hospital (University of Delhi), Dilshad Garden, Delhi, 110095, India

    Diwesh Chawla

  4. Department of Medicine, University College of Medical Sciences and GTB Hospital (University of Delhi), Dilshad Garden, Delhi, 110095, India

    Rajnish Avasthi

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  1. Mohd Jahid
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Correspondence to Rafat Sultana Ahmed.

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Jahid, M., Rehan-Ul-Haq, Jha, P.K. et al. Tumor necrosis factor-α -308 polymorphism in North Indian rheumatoid arthritis patients and association with mRNA and serum TNF-α. Clin Rheumatol 36, 2209–2216 (2017). https://doi.org/10.1007/s10067-017-3774-7

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  • DOI: https://doi.org/10.1007/s10067-017-3774-7

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