Iranian journal of pathology · 2025
STAT4 (rs7574865) Polymorphism and Serum STAT4 Levels in Rheumatoid Arthritis Susceptibility, Severity, and Treatment Response: A Case-Control Study in Iraqi Patients.
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Abdalhussein Amna R, Zayed Karrar S
Аннотация
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.
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.