BMP15 genetic variations in patients with premature ovarian insufficiency – correlation with clinical and laboratory parameters

Objective : Bone morphogenetic protein 15 (BMP15) is an oocyte-specific protein with essential functions on early folliculogenesis, a regulator of granulosa cell growth and differentiation. Recognizing the significant role of BMP15 in the development of Premature Ovarian Insufficiency (POI), our objective was to study the incidence of its genetic variants in a group of Bulgarian women affected by POI and to correlate them with clinical-laboratory parameters of the patients. Materials and methods : Direct Sanger sequencing of the BMP15 gene was performed in 37 patients with POI. The prevalence of the variants was compared to the internal database with unselected Bulgarian individuals. Results : In 56.8% of the patients, we detected one or two of the following variants c.-9C>G, c.308A>G, c.852C>T and c.538G>A. A significantly increased frequency of heterozygotes for variants c.-9C>G (40.5%) and c.308A>G (29.7%) was established in POI patients. We found that the combined carriership of these two frequent variants is significantly associated with the increased levels of FSH and the duration of amenorrhea, in Bulgarian patients with POI. Conclusion : Our study underscores the significant role of BMP15 as a crucial candidate gene and emphasizes the need for investigations in diverse population groups for its inclusion in the algorithm for early diagnostics and management of patients with POI.