Positive correlation between Bax and Bcl-2 gene polymorphisms with the risk of endometriosis: A case-control study.

Background: Endometriosis is a chronic, gynecological disorder, and the disease's pathogenesis is still debatable. Genes related to apoptosis have been revealed to be deregulated in endometriosis.

Objective: This study investigates the relationship between polymorphic variants of Bax -248G $>$ A and Bcl-2 -938C $>$ A promoter regions with endometriosis risk in an Iranian population.

Materials and methods: In this case-control study, the polymorphisms of Bax -248G $>$ A and Bcl-2 -938C $>$ A promoter regions were analyzed in 127 Iranian cases and 125 controls who were referred to Ali-ibn-Abi Taleb Educational hospital, Zahedan, Iran between May 2022 and February 2023. The genotypic analysis was performed for all the subjects using the polymerase chain reaction-restriction fragment length polymorphism method.

Results: The frequencies of mutant allele A carriers and the A allele of Bax -248G $>$ A polymorphism showed about 2-fold significant increase of endometriosis risk (p = 0.04; p = 0.01, respectively). The frequencies of the mutant genotype AA and A allele carriers of Bcl-2 -938C $>$ A polymorphism were approximately 4 and 2.5-fold higher in endometriosis compared to the control women, which were highly significant (p $>$ 0.001). Moreover, the allele A frequency of Bcl-2 -938C $>$ A was associated with a 2-fold higher risk of endometriosis (p $>$ 0.001). Furthermore, the combination effects of these 2 single nucleotide polymorphisms showed that women with Bax -248G $>$ A GGand Bcl-2 -938C $>$ A AA variant alleles were associated with about 5 times higher risk of endometriosis (p $>$ 0.001). Notably, a significant difference was observed in mutant allele distribution between minimal/mild (stage I and II) and moderate/severe (stage III and IV) women with endometriosis disease.

Conclusion: The results of our study provide evidence that Bcl-2 -938C $>$ A and Bax -248G $>$ A single nucleotide polymorphisms might be associated with the risk of endometriosis.