The Impact of FSHR Gene Polymorphisms Ala307Thr and Asn680Ser in the Endometriosis Development

Endometriosis is an estrogen-dependent inflammatory disease that affects a large number of women in reproductive age. Follicle-stimulating hormone (FSH) plays a role in steroidogenesis and acts through a transmembrane glycoprotein, FSH receptor (FSHR). Polymorphisms in FSHR gene were previously associated with variability in FSH serum level and reproductive outcomes, but its relation with endometriosis has not been clarified and demonstrated conflicting results, ranging from strong links to no association to endometriosis. Inspired by these findings, we aimed to investigate the influence of FSHR Ala307Thr and Asn680Ser polymorphisms in the risk of endometriosis development and/or progression and the status of fertility in 352 women with endometriosis and 510 fertile controls. Single-marker analysis revealed no significant difference for both Ala307Thr and Asn680Ser polymorphisms between overall endometriosis and control group. However, when the endometriosis group was subdivided according to fertility status and disease stage, a positive association was found between 680Ser/Ser or GG genotype of the Asn680Ser polymorphism and fertile women with endometriosis (p = 0.004). Combined alleles of FSHR polymorphisms revealed that "GG/307Ala680Ser" was more frequently found in fertile women with endometriosis (haplotype frequency of 45.4% in fertile women with endometriosis and 38.3% in controls, p = 0.041). The combined alleles of FSHR polymorphisms disclosed that "GG/307Ala680Ser" was more frequently found in fertile women with endometriosis (haplotype frequency of 45.4% in fertile women with endometriosis and 38.3% in controls, p = 0.049), while "GA/307Ala680Asn" haplotype was less frequently found in endometriosis group (haplotype frequency of 6.5% in cases and 11.9% in controls, p = < 0.001), regardless of fertility status and stage of the disease. The findings suggest that 680Ser-Ser/GG genotype and "GG/307Ala680Ser" haplotype increase the risk of endometriosis in fertile women, while "GA/307Ala680Asn" haplotype decreases the risk of endometriosis development and progression.