Iranian Journal of Pathology

STAT4 (rs7574865) Polymorphism and Serum STAT4 Levels in Rheumatoid Arthritis Susceptibility, Severity, and Treatment Response: A Case-Control Study in Iraqi Patients

Document Type : Original Research

Authors

Amna R. Abdalhussein
Karrar Saleem Zayed

Department of Laboratory Investigations, Faculty of Science, University of Kufa, Najaf, Iraq

https://doi.org/10.30699/ijp.2025.2064449.3485
Abstract
Background & Objective: Signal Transducer and Activator of Transcription 4 (STAT4) is a key transcription factor involved in immune signaling pathways and has been implicated in susceptibility to rheumatoid arthritis (RA) across various populations. However, its role in Iraqi Arab cohorts remains largely unexplored.
Methods: A case–control study was conducted including 68 RA patients and 39 age- and sex-matched apparently healthy individuals. The association between the STAT4 (rs7574865) polymorphism, serum STAT4 levels, RA susceptibility, and therapeutic response to methotrexate (MTX), MTX + infliximab, and tofacitinib was investigated using PCR–RFLP and ELISA techniques.
Results: The frequencies of the GT and (GT+TT) genotypes were significantly higher among RA patients than in controls under codominant and dominant models (P = .003 and P < .001, respectively). The T allele was also significantly more frequent in RA patients than in healthy individuals (P = .001). GT and TT genotypes were significantly associated with severe disease (P = .042) and poor response to tofacitinib compared with the GG genotype (P = .042). Serum STAT4 levels were markedly elevated in RA patients compared with controls (P = .01), particularly in those with severe RA (P = .042).
Conclusion: The STAT4 rs7574865 T allele may contribute to increased susceptibility to RA, greater disease severity, and reduced responsiveness to tofacitinib therapy in Iraqi patients.

Keywords

Rheumatoid arthritis
STAT4
Polymorphism
PCR–RFLP
Methotrexate

Subjects

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Iranian Journal of Pathology
Volume 20, Issue 4
Summer 2025
Pages 421-430

  • Receive Date 03 May 2025
  • Revise Date 06 June 2025
  • Accept Date 21 July 2025

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