Zhang Shun, Wang Qing-Ming, Ding Xian-Ping, Wang Tao, Mu Xue-Mei, Chen Zu-Yi
Key Laboratory of Bio-Resources and Eco-Environment, Ministry of Education, School of Life Science, Institute of Medical Genetics, Sichuan University, Chengdu, China; Bio-resource Research and Utilization, Joint Key Laboratory of Sichuan and Chongqing, Chengdu, China.
Key Laboratory of Bio-Resources and Eco-Environment, Ministry of Education, School of Life Science, Institute of Medical Genetics, Sichuan University, Chengdu, China; Bio-resource Research and Utilization, Joint Key Laboratory of Sichuan and Chongqing, Chengdu, China; Institute of Medical Genetics, College of Life Science, Sichuan University, Chengdu 610064, China.
J Reprod Immunol. 2016 Nov;118:54-60. doi: 10.1016/j.jri.2016.08.007. Epub 2016 Sep 1.
Idiopathic Asthenozoospermia (AZS) is a common symptom of male infertility described as reduced forward motility or absence of sperm motility. The PATE1 is generally expressed in male genital tract and related to sperm development, maturation and fertilization. However, the single nucleotide polymorphisms (SNPs) of the PATE1 gene which contribute to AZS were still unknown. For this reason, the possible association between the single nucleotide polymorphisms of the PATE1 gene and idiopathic asthenozoospermia was investigated in this research.
108 idiopathic asthenozoospermia were screened by karyotype analysis, detection of Y microdeletions and mutations in 5 other genes from 140 clinical AZS. The sequence analyses of the PATE1 gene were conducted in 108 idiopathic asthenozoospermia and 106 fertile men with normospermic parameters in Sichuan, China.
In this study, a total 108 patients without chromosomal abnormalities, Y microdeletions and selected genes mutation were confirmed. The 1423G (odds ratio [OR] 1.939, 95% confidence interval [CI] 1.320-2.848, P=0.001) was found to be increased significantly in idiopathic asthenozoospermic patients compared with their fertile counterparts. This mutation substitutes a highly conserved glutamic to arginine at the position of the 47th amino acid which was shown to be located on the flank of the pleated sheet domain in PATE1 protein by the 3D model given by the Protein Model Portal (PMP). Moreover, PolyPhen-2 analysis predicted that this variant was "probably damaging".
These results suggested that PATE1 variant (A1423G) was probably one of the high risk genetic factors for idiopathic asthenozoospermia among males in Sichuan, China.
特发性弱精子症（AZS）是男性不育的常见症状，表现为精子前向运动能力降低或精子无运动能力。PATE1通常在男性生殖道中表达，与精子发育、成熟和受精有关。然而，PATE1基因中导致AZS的单核苷酸多态性（SNP）尚不清楚。因此，本研究调查了PATE1基因单核苷酸多态性与特发性弱精子症之间可能存在的关联。
从140例临床AZS患者中，通过核型分析、Y微缺失检测以及其他5个基因的突变检测，筛选出108例特发性弱精子症患者。对中国四川的108例特发性弱精子症患者和106例精子参数正常的可育男性进行了PATE1基因的序列分析。
在本研究中，共确认了108例无染色体异常、Y微缺失及所选基因突变的患者。与可育男性相比，特发性弱精子症患者中1423G（优势比[OR]1.939，95%置信区间[CI]1.320 - 2.848，P = 0.001）显著增加。该突变在第47位氨基酸位置将高度保守的谷氨酸替换为精氨酸，蛋白质模型门户（PMP）给出的三维模型显示该位置位于PATE1蛋白的β折叠结构域侧翼。此外，PolyPhen - 2分析预测该变异“可能有害”。
这些结果表明，PATE1变异（A1423G）可能是中国四川男性特发性弱精子症的高风险遗传因素之一。
