Parada-Bustamante Alexis, Lardone María Cecilia, Valdevenito Raúl, Ebensperger Mauricio, López Patricia V, Madariaga Marcia, Piottante Antonio, Castro Andrea
Institute of Maternal and Child Research, School of Medicine, University of Chile, Santa Rosa 1234, Santiago, Chile.
J Androl. 2012 Jan-Feb;33(1):88-95. doi: 10.2164/jandrol.110.012195. Epub 2011 Mar 10.
Androgens are essential for spermatogenesis. It has been postulated that androgen activity is modulated directly or indirectly by genetic variability in the androgen receptor gene sequence, including CAG/GGN polymorphisms and single-nucleotide polymorphisms (SNP). In this study, the frequency of 6 SNPs that constitute a haplotype in the androgen receptor sequence was determined by enzyme restriction assays and allele-specific polymerase chain reactions in 117 secretory azo/oligozoospermic men (93 idiopathic and 24 excryptorchidic), and in 121 controls with normal spermatogenesis (42 obstructive and 79 normozoospermic men) whose hormonal measurements and length of CAG/GGN polymorphisms were previously determined. The frequency of these 6 SNPs was not different between patients and controls. A total of 10 haplotypes (HAPs 1-10) formed by these 6 SNPs were found, and one of these haplotypes was observed with high frequency in the total population (HAP1, 83.2%; P < .001, χ(2) test). The frequency of the 10 haplotypes was not different between patients and controls, except for HAP5, which was only detected in one patient with a history of bilateral cryptorchidism (P = 0.014, Bonferroni test). On the other hand, no associations were found between the haplotypes studied and shorter or longer CAG or GGN polymorphisms. Interestingly, we found that the CAG 21 allele, which was previously correlated with an increased risk of idiopathic spermatogenic impairment, was more frequently found among the less common haplotypes that have higher follicle-stimulating hormone serum levels. In summary, we did not find an increased frequency of particular haplotypes in infertile men with idiopathic spermatogenic impairment compared with control men; however, we found that the CAG 21 allele, which appears to be associated with male infertility, is observed at a significantly higher proportion among the less common androgen receptor haplotypes.
雄激素对于精子发生至关重要。据推测，雄激素活性直接或间接受到雄激素受体基因序列中遗传变异的调节，包括CAG/GGN多态性和单核苷酸多态性（SNP）。在本研究中，通过酶切分析和等位基因特异性聚合酶链反应，测定了117例分泌性无精子症/少精子症男性（93例特发性和24例隐睾症患者）以及121例精子发生正常的对照者（42例梗阻性和79例正常精子症男性）中构成雄激素受体序列单倍型的6个SNP的频率，这些对照者的激素测量值和CAG/GGN多态性长度此前已确定。患者和对照者之间这6个SNP的频率没有差异。由这6个SNP形成了总共10种单倍型（单倍型1 - 10），其中一种单倍型在总人群中出现频率较高（单倍型1，83.2%；P <.001，χ²检验）。除了仅在一名有双侧隐睾病史的患者中检测到的单倍型5外，患者和对照者之间10种单倍型的频率没有差异（P = 0.014，Bonferroni检验）。另一方面，所研究的单倍型与较短或较长的CAG或GGN多态性之间未发现关联。有趣的是，我们发现先前与特发性生精功能障碍风险增加相关的CAG 21等位基因，在卵泡刺激素血清水平较高的较罕见单倍型中更常见。总之，与对照男性相比，我们未发现特发性生精功能障碍不育男性中特定单倍型的频率增加；然而，我们发现与男性不育相关的CAG 21等位基因在较罕见的雄激素受体单倍型中所占比例显著更高。
