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

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. Data Availability No datasets were generated or analysed during the current study.

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The authors would like to thank the study participants for their cooperation and the clinical staff at the gynecology and infertility clinics of Zahedan University of Medical Sciences for their assistance with patient recruitment. Funding This work was supported by a grant (Grant No. 10898) from Zahedan University of Medical Sciences, Zahedan, Iran. Author information Authors and Affiliations Contributions D.J. and M.T. conceived and designed the experiments. D.J., F.F. and M.R. analyzed the data. D.J. and M.R. performed the genotyping. D.J. and M.T. wrote the first draft of the manuscript. F.F. and M.R. contributed to the writing of the manuscript. All authors reviewed and approved the final manuscript. Corresponding authors Ethics declarations Competing Interests The authors declare no competing interests. Ethical Approval Ethical approval was obtained from the Ethics Committee of Zahedan University of Medical Sciences (Ethical code: IR.ZAUMS.REC.1402.438), in accordance with the Declaration of Helsinki. Consent to Publish Not applicable. Consent to Participate Not applicable. Clinical Trial Number Not applicable. Additional information Publisher’s Note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. Rights and permissions Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law. About this article Cite this article Jahantigh, D., Taheri, M., Forghani, F. et al. Synergistic Effects of IL17A rs2275913 and IL17F rs763780 on Endometriosis Risk and Severity. Bratisl. Med. J. (2026). https://doi.org/10.1007/s44411-026-00791-z Received: Revised: Accepted: Published: Version of record: DOI: https://doi.org/10.1007/s44411-026-00791-z