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中国西北部精索静脉曲张不育男性谷胱甘肽S-转移酶M1、T1和P1的基因多态性及氧化损伤评估

Genetic polymorphisms of glutathione S-transferase M1, T1, and P1, and the assessment of oxidative damage in infertile men with varicoceles from northwestern China.

作者信息

Tang Kaifa, Xue Wei, Xing Yao, Xu Shaoyuan, Wu Qifei, Liu Ruizhe, Wang Xinyang, Xing Junping

机构信息

Department of Urology, First Affiliated Hospital, School of Medicine, Xi'an Jiaotong University, Xi'an 710061, China.

出版信息

J Androl. 2012 Mar-Apr;33(2):257-63. doi: 10.2164/jandrol.110.012468. Epub 2011 May 5.

DOI:10.2164/jandrol.110.012468
PMID:21546615
Abstract

Our objective was to investigate the genetic polymorphisms of the glutathione S-transferase M1, T1, and P1 genes (GSTM1, GSTT1, and GSTP1) and to assess the oxidative damage in infertile men with varicoceles from northwestern China. A total of 65 infertile men with varicoceles and 30 controls were included in the study. Multiplex polymerase chain reaction and polymerase chain reaction-restriction fragment length polymorphism analyses were used to identify the genotypes. Sperm DNA damage was assessed by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end-labeling (TUNEL). The levels of 8-hydroxy-2'-deoxyguanosine (8-OH-dG) were measured by high-performance liquid chromatography with electrochemical detection. The activities of malondialdehyde (MDA) and nitric oxide (NO), and the total antioxidant capacity (TAC) were detected by spectroscopic analysis, and sperm characteristics were measured using computer-assisted semen analysis. The frequencies of the GSTM1, GSTT1, and GSTP1 genotypes were not significantly different between the control and patient groups (P > .05). The percentage of TUNEL-positive sperm and the levels of 8-OH-dG, MDA, and NO were higher but the sperm concentration and motility and the TAC were lower in the patients with the GSTM1, GSTT1, and GSTM1/T1 null genotypes than those in the patients with the GSTM1, GSTT1, and GSTM1/T1 present genotypes (P < .05). However, no significant differences were observed between the GSTP1 A/A and A/G+G/G genotypes (P > .05). Our results suggest that the GSTM1 and GSTT1 null genotypes may predispose sperm to increased oxidative damage in infertile men with varicoceles; however, GSTP1 allelic variation was not significantly different between the patient and control groups in this study.

摘要

我们的目的是研究谷胱甘肽S-转移酶M1、T1和P1基因(GSTM1、GSTT1和GSTP1)的基因多态性,并评估中国西北部患有精索静脉曲张的不育男性的氧化损伤情况。本研究共纳入65例患有精索静脉曲张的不育男性和30例对照。采用多重聚合酶链反应和聚合酶链反应-限制性片段长度多态性分析来鉴定基因型。通过末端脱氧核苷酸转移酶介导的dUTP-生物素缺口末端标记法(TUNEL)评估精子DNA损伤。采用高效液相色谱-电化学检测法测定8-羟基-2'-脱氧鸟苷(8-OH-dG)水平。通过光谱分析检测丙二醛(MDA)和一氧化氮(NO)的活性以及总抗氧化能力(TAC),并使用计算机辅助精液分析测量精子特征。对照组和患者组之间GSTM1、GSTT1和GSTP1基因型的频率无显著差异(P>.05)。与具有GSTM1、GSTT1和GSTM1/T1存在基因型的患者相比,具有GSTM1、GSTT1和GSTM1/T1缺失基因型的患者中,TUNEL阳性精子的百分比以及8-OH-dG、MDA和NO的水平较高,但精子浓度、活力和TAC较低(P<.05)。然而,GSTP1 A/A和A/G+G/G基因型之间未观察到显著差异(P>.05)。我们的结果表明,GSTM1和GSTT1缺失基因型可能使患有精索静脉曲张的不育男性的精子更容易受到氧化损伤;然而,在本研究中,患者组和对照组之间GSTP1等位基因变异无显著差异。

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