FSHR polymorphisms are associated with premature ovarian insufficiency development

Abstract

To evaluate the incidence of polymorphisms Asn680Ser (rs6166) and Ala307Thr (rs6165) of the FSHR gene and the occurrence of chromosomal abnormalities in woman with Premature Ovarian Insufficiency (POI) and in a control group and correlate the genetic and clinical findings. Case control study. A group of 103 infertile and patients with POI was selected trough clinical history and serum levels of the hormone FSH.The control group included 101 women with no familial history of POI and normal age of menopause.The genotyping of polymorphisms Asn680Ser (rs6166) and Ala307Thr (rs6165) of the FSHR gene was performed in both groups using TaqMan by PCR real time. Cytogenetic analysis was performed only in the group of patients with POI. 40 methaphases were evaluated through G banding technique. The karyotype analysis performed in patients POI showed that 98.05% (101/103) presented normal karyotype 46,XX, 1.95% (2/103) showed and increased heterochromatin region in the 9 and 16 chromosomes (46,XX,9qh+;46,XX,16qh+) both considered normal variations in the population.The genotyping for polymorphisms Ala307Thr demonstrated a statistically significant difference between the allele Ala of the polymorphism Ala307Thr, and a p value of 0.035, comparing the POI group with the control group. The analysis of Asn680Ser polymorphism incidence in patients and control group showed a non significant difference between them (p=0.094). The average levels of FSH hormone in POI patients in this study was 57.8mUI/mL. We concluded that most patients with POI and no other phenotypical alteration have normal karyotype, and they do not suspect of POI untill testing fertility. Also, we observed that the polymorphic allele Ala from Ala307Thr polymorphism showed statistically significant difference between patients with POI and control group, being more present in patients with POI, suggesting an important rule of FSHr in the regulation of folliculogenesis.