Leptin G2548 A and Leptin Receptor Q223R Gene Polymorphisms are Associated with an Increased Risk of Endometriosis

Background Endometriosis (EM) is defined as gynecological chronic inflammation and the presence of active foci of uterine mucous membrane outside the uterine cavity. Susceptibility to endometriosis is influenced by single nucleotide polymorphisms (SNPs) in intronic or intergenic regions. This study aimed to analyze the frequencies of genotypes and alleles of LEP G2548A (rs7799039) of the LEP gene and LEPR Q223R (rs1137101) of the LEPR gene to investigate their contributions to the pathogenesis of endometriosis.

Peripheral blood samples of 178 endometriosis patients and 160 healthy donors were isolated from peripheral blood leukocytes. Polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) techniques were used. A novel Bioinformatics analysis was undertaken to anticipate the potential roles of these polymorphisms.

The LEP rs7799039 AA genotype and mutant allele (A) were frequent in EM women as compared to healthy subjects (OR = 2.35, p = 0.024; OR = 1.35, p = 0.048, respectively). The LEPR rs1137101 mutant GG genotype mutant allele (G) was related to an increased risk of endometriosis (OR=3.22, p = 0.003; OR=1.45, p = 0.022, respectively). The combination of mutant AA and GG genotypes of LEP and LEPR SNPs showed an extremely adverse effect on disease susceptibility and more than ten times more susceptibility to EM. In addition, carriers of the mutant allele for LEP rs7799039 and LEPR rs1137101 polymorphism were more frequent in the moderate/severe (stage III and IV) group of the disease. The LEP G2548A (rs7799039) gene polymorphism may lead to varying allelic expression, as indicated by an in-silico research. Furthermore, bioinformatics analysis indicated that the LEPR Q223R (rs1137101) SNP will significantly alter its secondary structure and physicochemical properties.

Our research indicates that the LEP G2548A (rs7799039) and LEPR Q223R (rs1137101) polymorphisms may play a role in the pathophysiology of endometriosis. Considering the proven association between leptin signaling and endometriosis, these SNPs may function as potential indicators of disease risk. Similar content being viewed by others Data Availability The data presented in this study are available on request from the corresponding author.

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Author information Authors and Affiliations Contributions FF and DJ conceived and designed the experiments. DJ and MT analyzed the data. EKA and MR performed the genotyping. DJ and SGZ wrote the first draft of the manuscript. DJ performed bioinformatics analysis. FF, EKA, MR and MT contributed to the writing of the manuscript. All authors reviewed and approved the final manuscript. Corresponding authors Ethics declarations Competing interests The authors declare that they have no competing interests. Ethical Approval Ethical approval was obtained from the local Ethics committee of Zahedan University of Medical Sciences (Ethical code: IR.ZAUMS.REC.1401.080), in accordance with the Declaration of Helsinki. 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 Kiyani-Afzali, E., Forghani, F., Jahantigh, D. et al. Leptin G2548 A and Leptin Receptor Q223R Gene Polymorphisms are Associated with an Increased Risk of Endometriosis. Bratisl. Med. J. 126, 2024–2036 (2025). https://doi.org/10.1007/s44411-025-00186-6 Received: Revised: Accepted: Published: Version of record: Issue date: DOI: https://doi.org/10.1007/s44411-025-00186-6