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TNF-α –308G>A (rs1800629) Polymorphism and Thromboembolic Risk in Iraqi Patients with Warfarin-Treated Hematological Disorders: A Case-Control Study | ||
| Al-Kunooze Scientific Journal | ||
| Volume 12, Issue 3, July 2026, Pages 145-161 PDF (1.07 M) | ||
| Document Type: Original Article | ||
| DOI: 10.36582/ksj.2026.170630.1041 | ||
| Author | ||
| Esraa Sameer Al-fatlawey* | ||
| Kufa university -collage of science | ||
| Abstract | ||
| Tumor necrosis factor‑alpha (TNF‑α) is a complex pro‑inflammatory cytokine with notable pro‑coagulant characteristics. The TNF‑α promoter polymorphism (rs1800629) is a functional gain‑of‑function mutation associated with increased cytokine production and altered immunological responses. The impact of thromboembolic risk in warfarin‑treated hematological patients in Iraq is still unclear. This prospective case‑control study included 320 Iraqi patients undergoing chronic warfarin therapy for hematological diseases and 280 healthy controls. Genotyping of TNF‑α –308G>A was conducted by ARMS‑PCR. Clinical outcomes, including thromboembolic events, bleeding incidents, and time in therapeutic range (TTR), were prospectively documented. Logistic and multiple linear regression were utilized for adjusted analysis. The frequency of the A allele was markedly higher in patients (21.7%) compared to controls (14.1%; OR = 1.68; 95% CI: 1.23–2.29; p = 0.001). Individuals with the A allele (GA + AA genotypes) demonstrated a 2.18‑fold increased 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 had a lower mean TTR (56.8 ± 14.9% vs. 64.3 ± 16.1% in GG carriers; p = 0.008). The TNF‑α genotype independently contributed partial R² = 0.031 to a six‑locus pharmacogenetic‑cytokine model for warfarin dosage (overall R² = 0.613). The TNF‑α–308A allele serves as an independent risk factor for thromboembolic events in Iraqi patients with warfarin‑treated hematological disorders. 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. | ||
| Keywords | ||
| TNF-α rs1800629; Cytokine polymorphism; Thromboembolic risk; Warfarin; Hematological disorders | ||
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