Lu Ningxia, Wu Bin, Xia Yankai, Wang Wei, Gu Aihua, Liang Jie, Lu Chuncheng, Song Lin, Wang Shoulin, Peng Yuzhu, Zhang Zhengdong, Wang Xinru
Key Laboratory of Reproductive Medicine, Institute of Toxicology, Nanjing Medical University, Nanjing, China.
Int J Androl. 2008 Sep;31(5):527-33. doi: 10.1111/j.1365-2605.2007.00804.x. Epub 2007 Jul 25.
Cytochrome P4501A1 (CYP1A1) is a key enzyme in phase I bioactivation of polycyclic aromatic hydrocarbons (PAHs), which have potential reproductive toxicity. The aim of this study was to investigate the association of the CYP1A1 polymorphisms with male infertility in a Han-Chinese population. We genotyped two polymorphisms, CYP1A12A and CYP1A12C, using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay in a hospital-based case-control study including 192 infertile patients with non-obstructive azoospermia or severe oligozoospermia and 226 fertile controls. We found that the genotype distribution of CYP1A12C was significantly different between the patients and the controls (p = 0.019). Analysis showed that CYP1A12C AG genotype was associated with a significantly decreased risk of male infertility [odds ratio (OR) = 0.56, 95% confidence interval (95% CI) = 0.36-0.86, p = 0.005] compared with the AA genotype. A statistically significantly decreased risk of male infertility was found to be associated with the CYP1A12C AG genotype plus GG genotype compared with CYP1A12C AA genotype (OR = 0.60, 95% CI = 0.40-0.91, p = 0.011). No significant association was detected between CYP1A1*2A polymorphism and male infertility. Haplotypic analysis showed a significantly increased risk of male infertility associated with the C-A haplotype compared with the T-A haplotype (OR = 1.98, 95% CI = 1.27-3.09), indicating a synergic effect of the two polymorphisms. Our results suggest that the CYP1A1 polymorphisms may contribute to the pathogenesis of male infertility in the Han-Chinese population.
细胞色素P4501A1（CYP1A1）是多环芳烃（PAHs）I相生物活化过程中的关键酶，而多环芳烃具有潜在的生殖毒性。本研究旨在探讨CYP1A1基因多态性与汉族人群男性不育症之间的关联。在一项基于医院的病例对照研究中，我们采用聚合酶链反应-限制性片段长度多态性（PCR-RFLP）分析法，对192例非梗阻性无精子症或严重少精子症的不育患者和226例生育能力正常的对照者进行了CYP1A12A和CYP1A12C这两种多态性的基因分型。我们发现，患者与对照者之间CYP1A12C的基因型分布存在显著差异（p = 0.019）。分析表明，与AA基因型相比，CYP1A12C AG基因型与男性不育风险显著降低相关[比值比（OR）= 0.56，95%置信区间（95%CI）= 0.36 - 0.86，p = 0.005]。与CYP1A12C AA基因型相比，CYP1A12C AG基因型加GG基因型与男性不育风险在统计学上显著降低相关（OR = 0.60，95%CI = 0.40 - 0.91，p = 0.011）。未检测到CYP1A1*2A多态性与男性不育之间存在显著关联。单倍型分析显示，与T-A单倍型相比，C-A单倍型与男性不育风险显著增加相关（OR = 1.98，95%CI = 1.27 - 3.09），表明这两种多态性具有协同作用。我们的研究结果表明，CYP1A1基因多态性可能与汉族人群男性不育症的发病机制有关。
