Shun Zhang1, Qing-Ming Wang1, Xian-Ping Ding2, Tao Wang1, Xue-Mei Mu1, Zu-Yi Chen1. 1. 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. 2. 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. Electronic address: brainding@scu.edu.cn.
Abstract
PURPOSE: 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. METHODS: 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. RESULTS: 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". CONCLUSIONS: These results suggested that PATE1 variant (A1423G) was probably one of the high risk genetic factors for idiopathic asthenozoospermia among males in Sichuan, China.
PURPOSE: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. METHODS: 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. RESULTS: 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". CONCLUSIONS: These results suggested that PATE1 variant (A1423G) was probably one of the high risk genetic factors for idiopathic asthenozoospermia among males in Sichuan, China.