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雄激素受体()-CAG三核苷酸重复长度与特发性男性不育:一项病例对照试验及荟萃分析。

Androgen receptor ()-CAG trinucleotide repeat length and idiopathic male infertility: a case-control trial and a meta-analysis.

作者信息

Mobasseri Narges, Babaei Faezeh, Karimian Mohammad, Nikzad Hossein

机构信息

Gametogenesis Research Center, Kashan University of Medical Sciences, Kashan, Iran.

出版信息

EXCLI J. 2018 Dec 17;17:1167-1179. doi: 10.17179/excli2018-1744. eCollection 2018.

Abstract

CAG trinucleotide repeats in androgen receptor () gene encode a polyglutamine tract in AR N-terminal transactivation domain. Studies have been conducted to evaluate the effect of CAG repeat length on male infertility, which have yielded contradictory results. This study aimed to explore the number of -CAG repeats in 150 fertile controls and 150 idiopathic infertile men, divided into four azoospermia, oligozoospermia, asthenozoospermia, and teratozoospermia subgroups. In addition, a meta-analysis was conducted based on previous studies to assess the association of the mentioned variation with male infertility in recent years. Polymerase chain reaction (PCR) targeting followed by an electrophoresis on polyacrylamide gel was used for -CAG genotype detecting. Moreover, a systematic search was performed in PubMed, Web of Science, Science Direct, and Google Scholar databases to collect eligible studies for meta-analysis purpose. According to the results, a significant association was observed between increased length of -CAG polymorphism and male infertility (< 0.0001). Furthermore, there were similar significant associations in the azoospermia (= 0.048), asthenozoospermia (= 0.013) and teratozoospermia (= 0.002) subgroups. In addition, meta-analysis on forty studies showed a significant association between -CAG polymorphism in the overall analysis (SMD= 0.199, 95 % CI= 0.112-0.287, <0.001) and the Caucasian subgroup (SMD= 0.151, 95 % CI= 0.040-0.263, 0.008). Our results elucidated that long stretches of CAG repeat might lead to AR dysfunction, contributing to male infertility especially in the Caucasian population.

摘要

雄激素受体(AR)基因中的CAG三核苷酸重复序列在AR N端反式激活结构域中编码一段多聚谷氨酰胺序列。已有研究评估CAG重复长度对男性不育的影响,但结果相互矛盾。本研究旨在探究150名生育力正常对照者和150名特发性不育男性中-CAG重复序列的数量,将不育男性分为无精子症、少精子症、弱精子症和畸形精子症四个亚组。此外,基于既往研究进行荟萃分析,以评估近年来上述变异与男性不育的关联。采用靶向聚合酶链反应(PCR)并在聚丙烯酰胺凝胶上进行电泳来检测-CAG基因型。此外,在PubMed、Web of Science、Science Direct和Google Scholar数据库中进行系统检索,以收集符合条件的研究用于荟萃分析。结果显示,-CAG多态性长度增加与男性不育之间存在显著关联(P<0.0001)。此外,在无精子症亚组(P=0.048)、弱精子症亚组(P=0.013)和畸形精子症亚组(P=0.002)中也存在类似的显著关联。此外,对40项研究的荟萃分析表明,在总体分析中-CAG多态性与男性不育之间存在显著关联(标准化均数差=0.199,95%可信区间=0.112-0.287,P<0.001),在白种人亚组中也存在显著关联(标准化均数差=0.151,95%可信区间=0.040-0.263,P=0.008)。我们的结果表明,长片段CAG重复可能导致AR功能障碍,从而导致男性不育,尤其是在白种人群中。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d55e/6341423/6f2443fae68b/EXCLI-17-1167-t-001.jpg

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