Background: Tumor necrosis factor‑alpha (TNF‑α) is a multifaceted pro‑inflammatory cytokine with significant pro‑coagulant properties. The TNF‑α promoter polymorphism (rs1800629) is a functional gain‑of‑function mutation linked to increased cytokine production and modified immune responses. The effect on thromboembolic risk in warfarin‑treated hematological patients in Iraq remains unclear.
Objectives: This prospective case‑control study encompassed 320 Iraqi patients taking chronic warfarin therapy for hematological diseases and 280 healthy. Genotyping of TNF‑α –308G>A was conducted by ARMS‑PCR. Clinical outcomes encompassing bleeding incidents, thromboembolic events, and time in therapeutic range (TTR) were prospectively recorded. Logistic and multiple linear regression were utilized for adjusted analysis.
Results: The A allele frequency was markedly elevated in patients (21.7%) relative to controls (14.1%; OR = 1.68; 95% CI: 1.23–2.29; p = 0.001). Individuals possessing A allele (GA + AA genotypes) exhibited a 2.18‑fold elevated risk of thromboembolic problems relative to GG homozygotes (adjusted OR = 2.18; 95% CI: 1.43–3.32; p = 0.001). TNF‑α –308A carriers exhibited a lower mean TTR (56.8 ± 14.9% vs. 64.3 ± 16.1% in GG carriers; p = 0.008). The TNF‑α genotype contributed an independent partial R² = 0.031 to a six‑locus pharmacogenetic‑cytokine model for warfarin dose (overall R² = 0.613).
Conclusion: the TNF‑α–308A allele constitute an independent risk factor for thromboembolic events in Iraqi patients undergoing warfarin‑treated hematological illness. Genotyping of TNF‑α may pinpoint high‑risk patients requiring enhanced vigilance and regular INR monitoring. These findings support integrating cytokine gene profiling with pharmacogenetic testing in tailored anticoagulation approaches in the Middle East.