Are FSHR polymorphisms risk factors to premature ovarian insufficiency?

Premature ovarian insufficiency (POI) is an ovarian dysfunction characterized by increased FSH levels and amenorrhea before 40 years old. In recent years, the search for genetic causes of POI intensified and studies have been published relating the presence of mutations and polymorphisms in genes associated with development, recruitment and oocyte atresia. The aim of this study was to evaluate the presence of FSHR polymorphisms in our population and contribute with the elucidation of POI etiology. To achieve it, we have studied 100 patients with POI (G1), 60 patients with border line levels of FSH (G2) and 123 controls with regular menopause onset. Cytogenetic analysis of patients' samples and genotyping of Asn680Ser and Ala307Thr polymorphisms were performed in cases and controls. Cytogenetic analysis showed that 92% of G1 patients had normal karyotype, 4% presented polymorphic variants, 3% presented mosaic karyotype involving X chromosome. In G2, 91.6% had normal karyotype results, 3.2% displayed polymorphic variants, and 3.3% presented a mosaic karyotype involving X chromosome. Statistical comparison showed that the polymorphic allele of Ala307Thr polymorphism is more frequent in patients than in controls (G1: p < 0.001 and G2: p = 0.0259). This association has not been previously reported. We concluded that Ala307Thr polymorphism in FSHR can be potentially associated to POI development and can be considered as a screening marker in patients with ovarian failure signals.

COMT polymorphism influences decrease of ovarian follicles and emerges as a predictive factor for premature ovarian insufficiency.

BACKGROUND: Estrogens are important factors in the female reproductive functions and are processed by a number of enzymes along their metabolic pathway. The COMT gene constitutes a crucial element in estrogen metabolism and is assumed to be involved in the development of Premature Ovarian Insufficiency (POI). This study aimed to determine whether the presence of the COMT Val/Met polymorphism (rs4680) is associated to the risk of developing POI. FINDINGS: In this case-control study, we evaluated 96 infertile women with POI and 120 fertile women as controls, after obtaining a detailed history of the disease and follicle-stimulating hormone measurements, besides karyotype determination and fragile-X premutation syndrome investigation. COMT (Val/Met) genotypes were identified by real time PCR (genotyping TaqMan assay), and the results were statistically analyzed. A statistically significant difference was found in the distribution of COMT genotypes (p = 0.003) and alleles (p = 0.015) between the POI patients and the control group. CONCLUSION: We were able to demonstrate a strong association between the COMT Val/Met polymorphism and the risk of premature ovarian insufficiency in the Brazilian women evaluated. However, further studies in larger populations are necessary to confirm these findings.