STAT۴ (rs۷۵۷۴۸۶۵) Polymorphism and Serum STAT۴ Levels in Rheumatoid Arthritis Susceptibility, Severity, and Treatment Response: A Case-Control Study in Iraqi Patients

Background & Objective: Signal Transducer and Activator of Transcription ۴ (STAT۴) 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 ۶۸ RA patients and ۳۹ age- and sex-matched apparently healthy individuals. The association between the STAT۴ (rs۷۵۷۴۸۶۵) polymorphism, serum STAT۴ 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 = .۰۰۳ and P < .۰۰۱, respectively). The T allele was also significantly more frequent in RA patients than in healthy individuals (P = .۰۰۱). GT and TT genotypes were significantly associated with severe disease (P = .۰۴۲) and poor response to tofacitinib compared with the GG genotype (P = .۰۴۲). Serum STAT۴ levels were markedly elevated in RA patients compared with controls (P = .۰۱), particularly in those with severe RA (P = .۰۴۲).Conclusion: The STAT۴ rs۷۵۷۴۸۶۵ T allele may contribute to increased susceptibility to RA, greater disease severity, and reduced responsiveness to tofacitinib therapy in Iraqi patients.

کلیدواژه ها:

Rheumatoid arthritis ، STAT۴ ، Polymorphism ، PCR–RFLP ، Methotrexate