A functional variant in the UBE2B gene promoter is associated with idiopathic azoospermia.
A functional variant in the UBE2B gene promoter is associated with idiopathic azoospermia.
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UBE2B 基因启动子的功能变异与特发性无精子症有关。
DOI：
10.1186/s12958-015-0074-4
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发表时间：
2015-07-30
期刊：
影响因子：
--
通讯作者：
Gui Y
中科院分区：
文献类型：
--
作者：
Mou L;Zhang Q;Diao R;Cai Z;Gui Y
多种遗传变异导致人类精子发生异常。泛素结合酶E2B（UBE2B）在精子发生中起着重要作用，因为UBE2b基因敲除的雄性小鼠是不育的。本研究对776例特发性无精子症（IA）患者和709例正常生育男性的UBE 2B基因外显子和启动子区进行测序，以探讨UBE 2B是否参与IA的发病机制。在外显子区域，在患者组中检测到两个新的同义变体。在启动子区，在患者组中鉴定出四种已知变体和四种新变体。在启动子区的新变体中，通过TRANSFAC软件分析，有3个位于特异性蛋白1（SP1）转录因子的结合位点。荧光素酶分析表明，一个杂合变体（Chr5.133706925 A > G）抑制SP1的转录调节活性。一种位于UBE 2B基因启动子区的新变异（Chr5.133706925 A > G）在中国人群中赋予IA高风险。这些结果支持UBE2B在IA发病机制中的作用。
A variety of genetic variants lead to abnormal human spermatogenesis. The ubiquitin-conjugating enzyme E2B (UBE2B) plays a significant role in spermatogenesis as Ube2b-knockout male mice are infertile. In this study, we sequenced the exon and promoter region of UBE2B in 776 patients diagnosed with idiopathic azoospermia (IA) and 709 proven fertile men to examine whether UBE2B is involved in the pathogenesis of IA. In the exon region, two novel synonymous variants were detected in the patient group. In the promoter region, four known variants and four novel variants were identified in the patient group. Of the novel variants in the promoter region, three were located at the binding site of specificity protein 1 (SP1) transcription factor analyzed by TRANSFAC software. Luciferase assays demonstrated that one heterozygous variant (Chr5.133706925 A > G) inhibited the transcriptional regulation activity of SP1. A novel variant (Chr5.133706925 A > G) residing in the UBE2B gene promoter region confers a high risk for IA in a Chinese population. These results support a role for UBE2B in the pathogenesis of IA.