Gaikwad A, Khan S, Kadam S, Kadam K, Dighe V, Shah R, Kulkarni V, Kumaraswamy R, Gajbhiye R
Department of Clinical Research, National Institute for Research in Reproductive Health, Mumbai, India.
Department of Anatomy and Developmental Biology, Monash University, VIC, 3800, Australia.
Andrologia. 2018 Mar;50(2). doi: 10.1111/and.12858. Epub 2017 Aug 3.
The aim of the study was to detect the frequency of the CFTR gene variants poly-T, TG repeats and c.1408A>G p.Met470Val (M470V) in Indian men with congenital bilateral absence of the vas deferens (CBAVD). Men diagnosed with CBAVD (n = 76), their female partners (n = 76) and healthy men from general population (n = 50) were recruited. Genomic DNA was isolated and the polymorphic regions of IVS9- c.1210-12T [5] and M470V were amplified using specific primers followed by Sanger's DNA sequencing. A statistically significant increase in the frequency of heterozygous IVS9- c.1210-12T [5] (39.4%) was observed in CBAVD men as compared to controls (14%). The allelic distribution of c.1210-12T [5], c.1210-12T [7] and c.1210-12T [9] in CBAVD men was 21%, 64.4% and 13% and that in healthy controls was 7%, 73% and 20% respectively. Longest TG repeat c.1210-34TG [13] was found in association with c.1210-12T [5] with an allelic frequency of 5.9% in CBAVD men. We found a significant association of c.1210-34TG [12]/c.1210-34TG [13] - c.1210-12[5] -V470 allele in CBAVD men. Twelve female partners harboured a heterozygous c.1210-12T [5] allele. The study emphasises the need to screen both partners for the polymorphisms M470V, poly-T, TG tract repeats in addition to population-specific known CFTR gene mutations.
本研究旨在检测先天性双侧输精管缺如(CBAVD)的印度男性中CFTR基因变异多聚T、TG重复序列以及c.1408A>G p.Met470Val(M470V)的频率。招募了被诊断为CBAVD的男性(n = 76)、他们的女性伴侣(n = 76)以及来自普通人群的健康男性(n = 50)。分离基因组DNA,使用特异性引物扩增IVS9 - c.1210 - 12T [5]和M470V的多态性区域,随后进行桑格DNA测序。与对照组(14%)相比,CBAVD男性中杂合子IVS9 - c.1210 - 12T [5](39.4%)的频率有统计学意义的增加。CBAVD男性中c.1210 - 12T [5]、c.1210 - 12T [7]和c.1210 - 12T [9]的等位基因分布分别为21%、64.4%和13%,而健康对照组中分别为7%、73%和20%。在CBAVD男性中发现最长的TG重复序列c.1210 - 34TG [13]与c.1210 - 12T [5]相关联,等位基因频率为5.9%。我们发现CBAVD男性中c.1210 - 34TG [12]/c.1210 - 34TG [13] - c.1210 - 12[5] -V470等位基因存在显著关联。12名女性伴侣携带杂合的c.1210 - 12T [5]等位基因。该研究强调除了特定人群已知的CFTR基因突变外,还需要对伴侣双方进行M470V、多聚T、TG序列重复多态性的筛查。