Synergistic Effects of IL17A rs2275913 and IL17F rs763780 on Endometriosis Risk and Severity

Abstract

Endometriosis is a chronic inflammatory disorder with a complex genetic etiology. The interleukin-17 (IL-17) family, particularly IL-17 A and IL-17 F, plays a critical role in driving pro-inflammatory responses within the peritoneal cavity. This case-control study investigated the association of IL17A rs2275913 and IL17F rs763780 polymorphisms with endometriosis risk and severity in 208 surgically confirmed patients and 205 age-matched healthy controls from an Iranian population. Genotyping was performed using PCR-RFLP. Logistic regression analysis was used to assess associations with disease risk and clinical stage (I-II vs. III-IV). The IL17A rs2275913 AA genotype (OR = 1.98, 95% CI: 1.04–3.77, p = 0.038) and A allele (OR = 1.49, 95% CI: 1.10–2.02, p = 0.009) were associated with increased endometriosis risk. For IL17F rs763780, the AG (OR = 1.68, 95% CI: 0.98–2.88, p = 0.048) and GG (OR = 3.69, 95% CI: 1.00-13.60, p = 0.044) genotypes and the G allele (OR = 1.98, 95% CI: 1.26–3.12, p = 0.003) were significant risk factors. The combined GA (IL17A) / AG (IL17F) genotype showed an almost 8-fold increased risk (OR = 7.52, 95% CI: 2.16–26.19, p = 0.001). Both variant genotypes were significantly more frequent in moderate/severe (stage III-IV) than in minimal/mild disease (stage I-II) (p < 0.01). After Bonferroni correction (p < 0.025), the IL17A A allele, IL17F dominant model, IL17F G allele, the combined GA/AG genotype, and both severity associations remained significant. Our findings indicate that IL17A rs2275913 and IL17F rs763780 polymorphisms independently influence endometriosis susceptibility and may contribute to disease progression, serving as potential genetic biomarkers.