摘要
目的泛素水平与精子数量的质量存在明显的相关。X染色体连锁的泛素特异蛋白酶26（USP26）基因在人类睾丸中特异表达，其变异与精子发生的关系存在争议。本研究旨在研究中国汉族男性USP26基因的多态性分布及其与男性不育的关系。方法用基因组DNA测序的方法分析221例不育男性（包括无精子症、弱精子症、少精子症和少弱精子症患者）和101正常生育男性的USP26基因全序列，分析其多态性和基因型在不同类型患者与生育对照之间的差异。结果本研究共发现6个变异位点：370—371insACA、494T〉C、508G〉A、576G〉A、1044T〉A和1423C〉T，对应的氨基酸改变分别为T123．124ins、L165S、G170R、E192E、F348L和H475Y。其中576G〉A（E192E）为同义突变，其氨基酸序列没有改变。508G〉A（G170R）为首次发现，其余5种变异在先前的研究中已有报道。与猕猴基因组比较发现370．371insACA和494T〉C为回复突变。576G〉A在正常生育组中高达78．2％，明显高于不育男性的49．1％（P〈0．01）；其余5个位点在不育和生育人群中没有明显差异（P〉0．05）。本研究共发现9种USP26基因型。在不育与生育人群的主要基因型有370insACA＋494C＋1423T、576A和576G型。576A和576G型在不育与生育人群中的分布存在明显差异（P〈0．01），而370insACA＋494C＋1423T型没有统计学差异（P〉0．05）。576A型在正常精子活力组明显高于低活力组（P〈0．05）；576G型在弱精子组明显低于正常生育男性对照（P〈0．01）；370insACA＋494C＋1423T型在不同精子密度和精子活力组间均没有明显差异（P〉0．05）。结论我国汉族人群中USP26基因370insACA＋494C＋1423T串突变与精子发生没有直接关系。USP26基因576G〉A位点的同义SNPs在不同精子活力组间有显著差异，576A可能有潜在的促进精子活力的作用。
Objective Increased sperm ubiquitin was inversely associated with sperm count and motility. Ubiquitin-specific protease 26 （USP26）, which is an X-linked gene, has been studied as a potential infertility gene. There are conflicting reports on whether variations in USP26 are associated with spermatogenesis.Methods In order to assess that USP26 polymorphisms contribute to male infertility, we screened 221 infertile men with azoospermia, oligozoospermia, asthenozoospermia, or oligoasthenozoospermia, and 101 control fertile men using DNA sequencing. Results There were six polymorphisms identified, including an unreported variation （508G〉A, G170R）. Only the allele frequency of 576G〉A was significantly higher in fertile men than infertile patients （p 〈 0.001）, although this variant does not result in an amino acid change. The major haplotypes in fertile and infertile men were 576A （76.2% vs 47.5% of the population, p 〈 0.001）, 576G （14.9% vs 39.4%, p 〈 0.001）, and 370-371insACA, 494C, 1423T cluster （5.0% vs 8.6%, p = 0.248）. The haplotype 576A was under-transmitted, whereas the haplotype 576G was over- transmitted in infertile men with asthenozoosperrnia and oligoasthenozoospermia. Conclusions Our results indicated the variation of USP26 was not directly associated with human sperm count but suggested it might be a potential role in sperm motility. The 576G〉A synonymous single nucleotide polymorphism （SNP） might have a role in improving the sperm motility.
