CONACyT Research Fellow-Centro de Biotecnología Genómica, Instituto Politécnico Nacional, Laboratorio de Medicina de Conservación, Blvd. del Maestro S/N, Esq. Elías Piña, 88710, Reynosa, Tamaulipas, Mexico.
División de Genética, Centro de Investigación Biomédica de Occidente, Centro Médico Nacional de Occidente, Laboratorio de Bioquímica 1B, Instituto Mexicano del Seguro Social, Sierra Mojada 800, 44340, Guadalajara, Jalisco, Mexico.
J Assist Reprod Genet. 2018 Aug;35(8):1483-1488. doi: 10.1007/s10815-018-1232-3. Epub 2018 Jun 18.
Primary ovarian insufficiency (POI) is a clinical condition observed in women younger than 40 years of age, characterized by amenorrhea, hypoestrogenism, high levels of follicle-stimulating hormone (FSH), and infertility. Mutations in some master regulators of the development, maturation, and maintenance of ovarian follicles such as BMP15, FSHR, FOXL2, and GDF9 have been suggested as etiological factors in the development of POI. The aim of this study, the first in the Mexican population, is to evaluate the presence of mutations or polymorphisms in these four candidate genes.
In a sample of 20 Mexican patients with idiopathic POI, we looked for and analyzed genetic variants in BMP15, FSHR, FOXL2, and GDF9 genes.
We observed two polymorphisms: a coding change, c.919G>A (p.Ala307Thr), in the FSHR gene and a synonymous variant, c.447C>T (p.Thr149Thr), in the GDF9 gene. These two variants have been reported previously as polymorphisms (rs6165 and rs254286, respectively). We observed no significant difference associated with POI in the patients when compared with a healthy control group (p > 0.05). Also, no exonic variants were found for the genes BMP15 and FOXL2 in the individuals tested.
The lack of association of the evaluated genes in this sample of Mexican women is consistent with the complex genetic etiology of POI that is observed across cohorts studied thus far.
原发性卵巢功能不全（POI）是一种发生于 40 岁以下女性的临床病症，其特征为闭经、雌激素水平降低、卵泡刺激素（FSH）水平升高以及不孕。一些调节卵巢卵泡发育、成熟和维持的主调控因子（如 BMP15、FSHR、FOXL2 和 GDF9）的基因突变被认为是 POI 发病的病因学因素。本研究在墨西哥人群中首次开展，旨在评估这四个候选基因中是否存在突变或多态性。
在 20 例特发性 POI 墨西哥患者的样本中，我们寻找并分析了 BMP15、FSHR、FOXL2 和 GDF9 基因中的遗传变异。
我们观察到两种多态性：FSHR 基因中的编码改变 c.919G>A（p.Ala307Thr）和 GDF9 基因中的同义变体 c.447C>T（p.Thr149Thr）。这两种变体先前被报道为多态性（分别为 rs6165 和 rs254286）。与健康对照组相比，患者中未发现与 POI 相关的显著差异（p>0.05）。此外，在测试的个体中，未发现 BMP15 和 FOXL2 基因的外显子变异。
在本墨西哥女性样本中，评估基因缺乏关联与 POI 的复杂遗传病因一致，这在迄今为止研究的多个队列中均有观察到。
