Combined deletion of DAZ2 and DAZ4 copies of Y chromosome DAZ gene is associated with male infertility in Tunisian men
Combined deletion of DAZ2 and DAZ4 copies of Y chromosome DAZ gene is associated with male infertility in Tunisian men
复制标题
DOI：
10.1016/j.gene.2014.05.061
复制
发表时间：
2014-09-01
期刊：
影响因子：
3.5
通讯作者：
Ammar-Keskes, Leila
中科院分区：
文献类型：
--
作者：
Ghorbel, Myriam;Baklouti-Gargouri, Siwar;Ammar-Keskes, Leila
男性不育症与AZFc微缺失之间的关系因国家和人群而异，AZFc微缺失去除了Y染色体的多个基因。本研究的目的是分析突尼斯男性无精子症（DAZ）基因拷贝缺失的患病率和特点，及其与生精障碍和男性不育的关系。241名不育男性（30.7%无精子症（n = 74），31.5%少精子症（n = 76）和37.7%正常精子症（n = 91））和115名生育至少一个孩子的健康男性被纳入研究。采用聚合酶链反应（PCR）-限制性片段长度多态性和PCR分析了3个DAZ特异性单核苷酸变异位点和6个双等位基因DAZ-SNV（I-VI）。我们的发现显示不育男性的高频率（73.85%）和对照组（78.26%）只有3个DAZ基因拷贝（DAZ 1/DAZ 2/DAZ 3或DAZ 1/DAZ 3/DAZ 4变体）;因此，DAZ 2或DAZ 4缺失在不育患者中均较常见（分别为36.5%和37.3%）和可育组（分别为33.9%和44.3%），并且在不育组中，少精子症男性中DAZ 4拷贝的去除比正常精子症男性中显著更频繁（p = 0.04）。我们还首次报道了DAZ 2和DAZ 4拷贝同时缺失在不育男性中（12.4%）比在生育男性中（4.3%）更常见（p = 0.01）。然而，DAZ 1/DAZ 2和DAZ 3/DAZ 4簇的缺失非常罕见。对突尼斯人群DAZ基因拷贝数的分析表明，DAZ 2和DAZ 4基因拷贝数的同时缺失与男性不育有关，DAZ 4拷贝数的缺失似乎促进了少精症的发生。(C)2014爱思唯尔有限公司版权所有。
The relationship between male infertility and AZFc micro-deletions that remove multiple genes of the Y chromosome varies among countries and populations. The purpose of this study was to analyze the prevalence and the characteristics of different Deleted in azoospermia (DAZ) gene copy deletions and their association with spermatogenic failure and male infertility in Tunisian men. 241 infertile men (30.7% azoospermic (n = 74), 31.5% oligozoospermic (n = 76) and 37.7% normozoospermic (n = 91)) and 115 fertile healthy males who fathered at least one child were included in the study. Three DAZ-specific single nucleotide variant loci and six bi-allelic DAZ-SNVs (I-VI) were analyzed using polymerase chain reaction (PCR)-restriction fragment length polymorphism and PCR. Our findings showed high frequencies of infertile men (73.85%) and controls (78.26%) having only three DAZ gene copies (DAZ1/DAZ2/DAZ3 or DAZ1/DAZ3/DAZ4 variants); so deletion of DAZ2 or DAZ4 were frequent both in infertile (36.5% and 37.3%, respectively) and fertile groups (33.9% and 44.3%, respectively) and removing DAZ4 copy was significantly more frequent in oligospermic than in normospermic men (p = 0.04) in infertile group. We also report for the first time that simultaneous deletion of both DAZ2 and DAZ4 copies was significantly more common in infertile men (12.4%) than in fertile men (4.3%) (p = 0.01). However, deletions of DAZ1/DAZ2 and DAZ3/DAZ4 clusters were very rare. Analysis of DAZ gene copies in Tunisian population, suggested that the simultaneous deletion of DAZ2 and DAZ4 gene copies is associated with male infertility, and that oligospermia seems to be promoted by removing DAZ4 copy. (C) 2014 Elsevier B.V. All rights reserved.