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

Autor(es)

Andre, Gustavo Mendonca ^[1] ; Trevisan, Camila Martins ^[1] ; Pedruzzi, Isabela Nacione ^[1] ; Martins Fernandes, Ramon Felix ^[1] ; Oliveira, Renato ^[1] ; Christofolini, Denise Maria ^[1] ; Bianco, Bianca ^[1] ; Barbosa, Caio Parente ^[1]

Afiliação do(s) autor(es)

^[1] Fac Med ABC, Human Reprod & Genet Ctr, Dept Collect Hlth, Ave Lauro Gomes 2-000, BR-09060870 Santo Andre - Brazil

• Tipo de documento: Artigo Científico
• Fonte: DNA AND CELL BIOLOGY; v. 37, n. 6 APR 2018.
• Citações Web of Science: 7

Resumo

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. (AU)

• Processo FAPESP: 17/01202-7 - Busca de mutações novas em genes candidatos ao desenvolvimento e progressão da endometriose por meio de sequenciamento de nova geração
• Beneficiário: Caio Parente Barbosa
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 16/25953-9 - Avaliação de mutações e/ou polimorfismos em genes candidatos por sequenciamento de nova geração em mulheres inférteis com e sem endometriose e sua correlação com resultados de estimulação ovariana controlada em tratamentos de reprodução humana assistida
• Beneficiário: Bianca Alves Vieira Bianco
• Modalidade de apoio: Auxílio à Pesquisa - Regular