Variants of the CLOCK gene affect the risk of idiopathic male infertility in the Han-Chinese population
Variants of the CLOCK gene affect the risk of idiopathic male infertility in the Han-Chinese population
复制标题
CLOCK基因变异影响汉族人群特发性男性不育的风险
DOI：
10.3109/07420528.2015.1056305
复制
发表时间：
2015
影响因子：
2.8
通讯作者：
Zhang J
中科院分区：
文献类型：
--
作者：
Shen Ouxi;Nie Jihua;Tong Jian;Zhang Jie;Shen Ouxi;Ding Xinliang;Xia Yankai;Wang Xinru;Zhang J
最近的实验动物研究表明，昼夜节律运动输出周期kaput蛋白基因(CLOCK)在精子功能和男性生育能力中起着关键作用。这项研究的目的是确定时钟基因的变异是否与特发性男性不育有关。这项研究包括478名特发性不育男性和194名完成体检的生育对照组男性。每个受试者都捐献了5 毫升的外周血液和一份精液样本。用标准放射免疫法测定血清中的睾酮和卵泡刺激素(FSH)。其余血样提取DNA，采用实时荧光定量聚合酶链式反应技术检测时钟基因rs1801260、rs3817444和rs3749474三个标记单核苷酸多态。采用计算机辅助精液分析系统对受试者的精液进行分析。结果表明：(A)与精液参数正常相关的rs1801260变异与特发性不育的风险显著相关，(B)与精液参数正常和异常相关的rs3817444变异也表明特发性不育的风险增加，(C)与精液参数正常和异常相关的rs3749474变异与男性不育风险无关。此外，特发性不孕症患者血清睾酮和FSH水平升高与Clock基因的三个变异体相关。研究结果表明，携带Clock基因变异的人类受试者与特发性男性不育有关，因此可能成为男性不育的危险因素。
Recent experimental animal studies suggested that the circadian locomotor output cycles kaput protein gene (CLOCK) has been reported to play a critical role in sperm function and male fertility. The aim of this study was to determine whether variants of the CLOCK gene are involved in idiopathic male infertility. The study included 478 idiopathic infertile men and 194 fertile controls who completed physical examinations. Each subject donated 5 ml of peripheral blood and a sample of semen in the ejaculate. An aliquot of each blood sample was used to separate the serum for the measurement of testosterone as well as follicular stimulating hormone (FSH) using the standard radioimmunoassay. The rest of the blood samples was used to extract the DNA for the assay of three tagging single-nucleotide polymorphisms of CLOCK gene, viz., rs1801260, rs3817444 and rs3749474, using the real-time fluorescence quantitative PCR. The ejaculate of each subject was used for semen analysis by computer-assisted semen analysis system. The results indicated: (a) the variant rs1801260 associated with normal semen parameters was linked to a significant increase in the risk of idiopathic infertility, (b) the variant rs3817444 associated with both normal and abnormal semen parameters also indicated an increased risk of idiopathic infertility, and (c) the variants rs3749474 associated with both normal and abnormal semen parameters, on the other hand, conferred no significant risk for male infertility. Furthermore, elevated serum testosterone and FSH levels were correlated with the three variants of CLOCK gene in idiopathic infertility. The findings demonstrate that the human subjects with variants of the CLOCK gene are associated with idiopathic male infertility and therefore may be applied as a risk factor of male infertility.