PDF(Pubmed)
Abstract：
A male factor, commonly associated with poor semen quality, is revealed in about 50% of infertile couples. CFTR gene (Cystic Fibrosis Transmembrane Conduction Regulator) variants are one of the common genetic causes of azoospermia-related male infertility. Notably, the spectrum and frequency of pathogenic CFTR variants vary between populations and geographical regions. In this work, we made an attempt to evaluate the allele frequency (AF) of 12 common CFTR variants in infertile Russian men and healthy individuals from different districts of Russia. Because of the limited number of population-based studies on Russian individuals, we characterized the population AFs based on data from the Registry of Russian cystic fibrosis (CF) patients. In addition to the CF patient registry, we estimated the local frequencies of the same set of variants based on the results of genotyping of CF patients in local biocollections (from St. Petersburg and Yugra regions). AFs of common CFTR variants calculated based on registry and biocollection data showed good concordance with directly measured population AFs. The estimated region-specific frequencies of CFTR variants allowed us to uncover statistically significant regional differences in the frequencies of the F508del (c.1521_1523del; p.Phe508del) and CFTRdele2,3(21kb) (c.54-5940_273+10250del21kb; p.Ser18ArgfsX) variants. The data from population-based studies confirmed previous observations that F508del, CFTRdele2,3(21kb), and L138ins (c.413_415dup; p.Leu138dup)variants are the most abundant among infertile patients, and their frequencies are significantly lower in healthy individuals and should be taken into account during genetic monitoring of the reproductive health of Russian individuals.
摘要：
男性因素，通常与精液质量差有关，在大约50%的不孕夫妇中被发现。CFTR基因（囊性纤维化跨膜传导调节因子）变异是无精子症相关男性不育的常见遗传原因之一。值得注意的是,致病性CFTR变异的频谱和频率因人群和地理区域而异.在这项工作中,我们试图评估俄罗斯不育男性和来自俄罗斯不同地区的健康个体中12种常见CFTR变异的等位基因频率(AF).由于对俄罗斯个人的基于人群的研究数量有限，我们根据俄罗斯囊性纤维化(CF)患者登记处的数据对人群AF进行了定性.除了CF患者登记，我们根据局部生物采集(来自圣彼得堡和尤格拉地区)CF患者的基因分型结果,估计了同一组变异的局部频率.基于注册和生物采集数据计算的常见CFTR变体的AF与直接测量的群体AF显示出良好的一致性。CFTR变体的估计区域特定频率使我们能够发现F508del（c.1521_1523del;p.Phe508del）和CFTRdele2,3（21kb）（c.54-5940_27310250del21kb；p.Ser18ArgfsX）变体的频率的统计显着区域差异。基于人群的研究数据证实了以前的观察结果，即F508del，CFTRdele2,3(21kb),和L138ins（c.413_415dup;p.Leu138dup）变体在不育患者中最丰富，在健康个体中，其频率显着降低，在对俄罗斯个体的生殖健康进行遗传监测时应予以考虑。
