Psoriasis, a chronic inflammatory dermatological condition, exhibits heterogeneous responses to anti-TNF therapies such as etanercept (ETN), underscoring the need for predictive biomarkers. This study investigated the association of interleukin-1 beta (IL-1β) gene promoter polymorphisms (rs1143623 C/G, rs752338864 C/G, and rs1143627 C/T) with ETN efficacy in 80 Iraqi patients with moderate to severe plaque psoriasis. Patients were categorized according to treatment response: responders achieved ≥ 75% reduction in the Psoriasis Area and Severity Index (PASI), whereas non-responders demonstrated ≤ 50% reduction. Post-treatment serum IL-1β levels were significantly higher in non-responders (50.35 ± 15.81 pg/mL) compared to responders (35.38 ± 10.35 pg/mL; p = 0.001). Genotyping revealed that the rs752338864 CC genotype was exclusively present in responders (25% vs 0% in non-responders; p = 0.001) and showed a strong inverse correlation with non-responder status (ϕ = −0.342; p = 0.003), as well as a greater reduction in PASI score (p = 0.01). Logistic regression further identified serum IL-1β concentration as an independent predictor of non-response (OR = 1.11; p = 0.0115). In contrast, the other investigated SNPs (rs1143623 C/G and rs1143627 C/T) showed no significant association with treatment response. These findings suggest that the rs752338864 CC genotype may indicate a positive response, whereas increased IL-1β levels could reflect resistance to therapy. Overall, this study sheds new light on psoriasis pharmacogenetics and demonstrates the potential for incorporating genetic and biomarker assessments into individualized treatment strategies.
