Reproductive Medicine Center, Department of Obstetrics and Gynecology, The First Affiliated Hospital of Anhui Medical University, Hefei 230032, China.
Reprod Biomed Online. 2012 Dec;25(6):627-34. doi: 10.1016/j.rbmo.2012.09.005. Epub 2012 Sep 16.
Protamine genes play important roles in DNA packaging within the sperm nucleus. In order to evaluate the association of PRM1, PRM2, KIT and KITLG variants with susceptibility to severely defective spermatogenesis, 309 male infertility patients (199 cases with non-obstructive azoospermia and 110 cases with severe oligozoospermia) and 377 controls were recruited in the Chinese Han population. This study genotyped 38 single-nucleotide polymorphisms (SNP) in PRM1, PRM2, KIT and KITLG using Sequenom iplex. The results showed that PRM1 variant rs35576928 (p.R34S) was significantly associated with severe oligozoospermia and played a protective role against the disease (P=0.0079, Bonferroni correction, OR 0.426). The dominant model (variant-containing genotypes) of the SNP was confirmed to protect against the occurrence of oligozoospermia (P=0.0078, Bonferroni correction, OR 0.387). Haplotype analysis of PRM1 and PRM2 in combination exhibited that haplotype TACCGGC exhibited a significant protective effect against the occurrence of oligozoospermia when compared with controls (P=0.002, Bonferroni correction, OR 0.602). Haplotype TACCTGC was strongly associated with risk of the clinical phenotype severe oligozoospermia (P=0.002, Bonferroni correction, OR 2.716). The findings indicated that PRM1 variant rs35576928 (p.R34S) was associated with severely defective spermatogenesis in the Chinese Han population. Male spermatogenic failure may be associated with gene variants. We demonstrated whether such genetic variation of PRM1 and PRM2 affected clinicopathological characteristics and conferred susceptibility to this entity. In this study, we found that PRM1 variant rs35576928 (Arg>Ser) played a protective role against severe oligozoospermia. The dominant model analysis (variant-containing genotypes) confirmed that the SNP was a risk factor of a spermatogenesis defect. Haplotype analysis of PRM1 and PRM2 showed that TACCGGC was a common factor protecting against severe oligozoospermia, while the haplotype TACCTGC was strongly associated with the risk of the severe oligozoospmeria. Our findings indicate that the PRM1 variant rs35576928 (Arg>Ser) is associated with spermatogenesis defect in the Chinese Han population.
鱼精蛋白基因在精子核内的 DNA 包装中发挥重要作用。为了评估 PRM1、PRM2、KIT 和 KITLG 变异与严重缺陷型精子发生易感性的关系，在中国汉族人群中招募了 309 名男性不育患者（199 名非梗阻性无精子症患者和 110 名严重少精子症患者）和 377 名对照者。本研究使用 Sequenomiplex 对 PRM1、PRM2、KIT 和 KITLG 中的 38 个单核苷酸多态性（SNP）进行了基因分型。结果表明，PRM1 变体 rs35576928（p.R34S）与严重少精子症显著相关，并对该疾病具有保护作用（P=0.0079，Bonferroni 校正，OR 0.426）。该 SNP 的显性模型（含变异的基因型）被证实可防止少精子症的发生（P=0.0078，Bonferroni 校正，OR 0.387）。PRM1 和 PRM2 的单体型分析表明，与对照组相比，单体型 TACCGGC 对少精子症的发生具有显著的保护作用（P=0.002，Bonferroni 校正，OR 0.602）。单体型 TACCTGC 与严重少精子症的临床表型风险密切相关（P=0.002，Bonferroni 校正，OR 2.716）。这些发现表明，PRM1 变体 rs35576928（p.R34S）与中国汉族人群中严重缺陷型精子发生有关。男性生精失败可能与基因变异有关。我们证明了 PRM1 和 PRM2 的这种遗传变异是否影响临床病理特征并导致对该实体的易感性。在这项研究中，我们发现 PRM1 变体 rs35576928（Arg>Ser）对严重少精子症有保护作用。显性模型分析（含变异的基因型）证实该 SNP 是精子发生缺陷的一个危险因素。PRM1 和 PRM2 的单体型分析表明，TACCGGC 是一种常见的保护严重少精子症的因素，而单体型 TACCTGC 与严重少精子症的风险密切相关。我们的研究结果表明，PRM1 变体 rs35576928（Arg>Ser）与中国汉族人群中的精子发生缺陷有关。
