Are FSHR polymorphisms risk factors to premature ovarian insufficiency?

Abstract

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.

Chinese abstract

卵巢功能不全（POI）的特征是女性在40岁前出现FSH水平的升高与闭经。近年来，有关POI病因的遗传学研究日益增多，研究发现基因的突变、多态性与卵泡的发育、募集、闭锁相关。本研究的目的在于评估FSHR多态性在人群中的表现，及其与POI病因的相关性。我们的研究包括100名POI患者（G1），60名FSH边缘水平的患者（G2）和123名正常绝经对照组患者（G3）。对病例和对照组中患者样本进行了细胞遗传学分析，与Asn680Ser和Ala307Thr多态性基因分型。基因分型分析显示，92%的G1组患者核型正常，4%表现出多态性改变，3%出现含X染色体的嵌合体核型。在G2中，91.6%的患者核型正常，3.2%表现为多态性改变，3.3%表现为含X染色体的嵌合体核型。统计学分析显示，Ala307Thr多态性等位基因在POI患者中的发生率高于对照组（G1： p＜0.001，G2：p = 0.0259）。该相关性此前从未被报道。我们认为，FSHR中Ala307Thr的多态性与POI的发生发展有潜在的联系，也许可以作为有卵巢早衰趋势患者的筛查标记物。

• Follicle stimulating hormone
• FSHR
• infertility
• premature ovarian insufficiency
• X chromosome

Declaration of interest

None of the authors has any conflict of interest to disclose.

We would like to thank CNPq for Research grant (#470333/2013-8) and Monise Santos scholarship.