Impact of Interleukin-6 Serum Levels and rs1800795 Promoter Polymorphism on Disease Activity and Tumor Necrosis Factor Inhibitor Efficacy in Rheumatoid Arthritis

Authors

  • Ahmed Hilal Kamel Department of Microbiology, College of Medicine, Al-Iraqia University, Baghdad, Iraq
  • Ahmed Abdul-Hassan Abbas Department of Microbiology, College of Medicine, Al-Nahrain University, Baghdad, Iraq
  • Yasameen Abbas Humadi Department of Internal Medicine, College of Medicine, Al-Nahrain University, Baghdad, Iraq https://orcid.org/0000-0002-0911-8318

DOI:

https://doi.org/10.54133/ajms.v9i1.2146

Keywords:

Interleukin-6, Rheumatoid arthritis, rs1800795 polymorphism, Tumor necrosis factor inhibitors

Abstract

Background: Rheumatoid arthritis (RA) is a systemic inflammatory disease. Gene polymorphisms of cytokines play a pivotal role in their pathogenesis and are able to modulate susceptibility and responsiveness for RA treatment. Objective: To investigate the serum expression of the rs1800795 variant of interleukin-6 (IL-6) and its association with disease severity and tumor necrosis factor (TNF)-α inhibitor response in RA. Methods: A case-control study was conducted, including 100 patients with RA and 100 healthy controls. Serum levels of IL-6 were measured. Genotyping of the IL-6 rs1800795 polymorphism was performed using TaqMan real-time PCR. Disease activity was assessed using the Clinical Disease Activity Index (CDAI), and treatment response was evaluated after six months of TNF inhibitor therapy. Results: Rheumatoid arthritis patients had significantly greater levels of IL-6 compared to the control group (p<0.001), with the diagnostic accuracy area under the curve (AUC) equal to 0.999. The mutant C allele of rs1800795 was significantly associated with increased RA risk (OR=1.70, p=0.022) and poor response to TNF inhibitors (OR=2.26, p=0.009). Higher IL-6 levels and the presence of the CC genotype were correlated with higher disease activity and lower treatment responsiveness (p<0.001). Conclusions: Elevated serum IL-6 levels and carriage of the IL-6 rs1800795 C allele are associated with susceptibility to RA, disease severity, and reduced response to TNF inhibitors. These findings prove the therapeutic potential of the IL-6 biomarker for patient stratification and optimized therapeutic strategies in RA therapy.

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2025-07-27

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Kamel, A. H., Abbas, A. A.-H., & Humadi, Y. A. (2025). Impact of Interleukin-6 Serum Levels and rs1800795 Promoter Polymorphism on Disease Activity and Tumor Necrosis Factor Inhibitor Efficacy in Rheumatoid Arthritis . Al-Rafidain Journal of Medical Sciences ( ISSN 2789-3219 ), 9(1), 118–126. https://doi.org/10.54133/ajms.v9i1.2146

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