Association of Interleukin 1 Receptor Antagonist (IL1RN) rs4251961 with Periodontitis Risk in Portuguese Postpartum Women: A Pilot Study

Periodontitis (PD), the second most prevalent oral disease, contributes to systemic health issues and results from a complex interaction between microbial dysbiosis and host immune responses, strongly shaped by genetic background. This pilot case–control study evaluated associations between five inflammation-related variants (IL1A rs1800587, IL1B rs1143634, IL1B rs16944, IL1RN rs4251961, TNFA rs1800629) and PD susceptibility in Portuguese postpartum women. Eighty-eight women (33 PD patients and 55 controls) were genotyped using iPLEX Gold technology. Associations were tested using logistic regression models, with multiple-testing correction applied to adjust significance thresholds. TNFA rs1800629 was associated with PD in the collapsed model (GA+AA vs. GG; OR = 3.3, p < 0.05). IL1RN rs4251961 showed strong associations across all models. In the codominant model, heterozygotes had increased PD odds (OR = 3.52, adjusted p < 0.05), while CC homozygotes showed 8-fold odds (OR = 8.1, adjusted p < 0.05). The collapsed model was also significant (p < 0.05). The remaining variants were not associated with PD. IL1RN rs4251961 may represent a novel genetic marker for PD, with clinical relevance given its inflammatory role and therapeutic use of recombinant IL-1RA in chronic inflammatory diseases. This first report linking IL1RN rs4251961 to PD supports validation in larger European cohorts.