Sequence variations of the EGR4 gene in Korean men with spermatogenesis impairment.
Sequence variations of the EGR4 gene in Korean men with spermatogenesis impairment.
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DOI：
10.1186/s12881-017-0408-5
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发表时间：
2017-05-02
影响因子：
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通讯作者：
Shim SH
中科院分区：
文献类型：
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作者：
Sung SR;Song SH;Kang KM;Park JE;Nam YJ;Shin YJ;Cha DH;Seo JT;Yoon TK;Shim SH
egr 4在成年小鼠睾丸中的初级和次级精母细胞中表达，并且在调节生殖细胞成熟中具有关键作用。Egr 4的功能丧失会阻断精子发生，显著减少产生的精子数量。在这项研究中，我们研究了EGR 4变异体是否存在于韩国男性精子发生障碍。共筛选了170名韩国男性精子发生障碍和272名正常对照。采用PCR-直接测序法对EGR 4基因编码区进行测序。我们在EGR 4基因的编码区和3′-UTR区鉴定了8个序列变异。4个为非同义变异（rs771189047、rs 561568849、rs763487015和rs 546250227），3个为同义变异（rs 115948271、rs 528939702和rs7558708），1个变异（rs 2229294）定位于3′-UTR。在对照中未检测到三种非同义变体[c.65_66InsG（p.Cys23Leufs *37）、c.236C > T（p.Pro79Leu）、c.1294G > T（p.Val432Leu）]和一种同义变体[c.1230G > A（p.Thr410）]。为了评估非同义变异的致病作用，我们使用了七种预测方法。通过SIFT和SNAP 2预测c.214C > A（p.Arg72Ser）和c.236C > T（p.Pro79Leu）变体是“破坏性的”。c.65_66insG（p.Cys23Leufs *37）变体通过突变品尝器、SNP &GO和SNAP 2预测为“致病”。c.867C > G（p.Leu289）变异体仅被Mutation Taster预测为“致病”。到目前为止，这项研究是第一个筛选与男性不育相关的EGR 4基因。然而，我们的研究结果并没有清楚地解释非同义EGR 4变异如何影响精子发生。因此，需要进一步的研究来验证EGR 4变异对精子发生的功能影响。本文的在线版本（doi：10.1186/s12881-017-0408-5）包含补充材料，可供授权用户使用。
Egr4 is expressed in primary and secondary spermatocytes in adult mouse testes and has a crucial role in regulating germ cell maturation. The functional loss of Egr4 blocks spermatogenesis, significantly reducing the number of spermatozoa that are produced. In this study, we examined whether EGR4 variants are present in Korean men with impaired spermatogenesis. A total 170 Korean men with impaired spermatogenesis and 272 normal controls were screened. The coding regions including exon-intron boundaries of EGR4 were sequenced by PCR-direct sequencing method. We identified eight sequence variations in the coding region and 3′-UTR regions of the EGR4 gene. Four were nonsynonymous variants (rs771189047, rs561568849, rs763487015, and rs546250227), three were synonymous variants (rs115948271, rs528939702, and rs7558708), and one variant (rs2229294) was localized in the 3′-UTR. Three nonsynonymous variants [c.65_66InsG (p. Cys23Leufs*37), c.236C > T (p. Pro79Leu), c.1294G > T (p. Val432Leu)] and one synonymous variant [c.1230G > A (p. Thr410)] were not detected in controls. To evaluate the pathogenic effects of nonsynonymous variants, we used seven prediction methods. The c.214C > A (p. Arg72Ser) and c.236C > T (p. Pro79Leu) variants were predicted as “damaging” by SIFT and SNAP2. The c.65_66insG (p. Cys23Leufs*37) variants were predicted as “disease causing” by Mutation Taster, SNPs &GO and SNAP2. The c.867C > G (p. Leu289) variants were predicted as “disease causing” only by Mutation Taster. To date, this study is the first to screen the EGR4 gene in relation to male infertility. However, our findings did not clearly explain how nonsynonymous EGR4 variations affect spermatogenesis. Therefore, further studies are required to validate the functional impact of EGR4 variations on spermatogenesis. The online version of this article (doi:10.1186/s12881-017-0408-5) contains supplementary material, which is available to authorized users.