Institute of Genetics and Hospital for Genetics Diseases, Osmania University, Begumpet, Hyderabad-500016, Andhra Pradesh, India.
Clin Chim Acta. 2009 Dec;410(1-2):43-7. doi: 10.1016/j.cca.2009.09.019. Epub 2009 Sep 26.
The CYP1A1 gene is a polymorphic gene and encodes for the CYP1A1 enzyme that catalyzes the bioactivation of polycyclic aromatic hydrocarbons (PAHs). PAHs are ubiquitous pollutants in the natural environment, which are capable of forming DNA adducts once being activated to generate DNA reactive metabolites. DNA adducts in sperm cells could be considered as a sign of severe DNA damage, which played an important role in meiotic division during spermatogenesis and could be associated with infertility. Lipophilic compounds undergo metabolic activation by phase I enzymes, which introduce a reactive center into the molecule, followed by phase II conjugation reaction resulting in a water soluble product.
We genotyped CYP1A1*2A, using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay in a hospital based case-control study including 206 infertile men and 230 healthy fertile (control) subjects.
Analysis showed that CYP1A12A CC genotype is associated with increased risk of male infertility (OR=6.08, 95% CI=1.91-25.27), while TC genotype showed a non-significantly increased risk of male infertility (OR=1.35 95% CI=0.89-2.05). Further, when the variant genotypes were combined (CYP1A12A TC+CC) assuming a co-dominant allele effect, TC plus CC genotypes were also found to be significant with increased risk of male infertility (OR=1.57 95% CI=1.05-2.35 p=0.02). Allele frequencies are calculated for each genotype of CYP1A1*2A and the differences for allele frequencies between the infertile and fertile men are determined using Fisher's exact test. T and C allele frequencies in infertile men are 71% and 29% as against 80% and 20% in fertile men. The differences for allele frequencies are found to be statistically significant (p=0.002). The results showed a drastic decrease in the sperm count and motility and increase in dead sperms in CC genotype when compared to other genotypes in infertile men.
Based on Indian study we conclude that CC genotype of CYP1A1 is associated in the pathogenesis of male infertility.
CYP1A1 基因是一个多态性基因，编码 CYP1A1 酶，该酶催化多环芳烃（PAHs）的生物活化。PAHs 是自然环境中普遍存在的污染物，一旦被激活生成 DNA 反应性代谢物，就能够形成 DNA 加合物。精子细胞中的 DNA 加合物可以被认为是严重 DNA 损伤的标志，在精子发生的减数分裂过程中发挥重要作用，并可能与不育有关。亲脂性化合物通过 I 相酶代谢激活，该酶在分子中引入一个反应中心，然后进行 II 相结合反应，生成水溶性产物。
我们使用聚合酶链反应-限制性片段长度多态性（PCR-RFLP）检测法，在一项包括 206 例不育男性和 230 例健康生育（对照）受试者的基于医院的病例对照研究中对 CYP1A1*2A 进行基因分型。
分析表明，CYP1A12A CC 基因型与男性不育的风险增加相关（OR=6.08，95%CI=1.91-25.27），而 TC 基因型则显示出男性不育的风险增加，但无统计学意义（OR=1.35，95%CI=0.89-2.05）。此外，当假设共显性等位基因效应将变体基因型组合（CYP1A12A TC+CC）时，TC 加 CC 基因型也被发现与男性不育的风险增加显著相关（OR=1.57，95%CI=1.05-2.35，p=0.02）。计算 CYP1A1*2A 各基因型的等位基因频率，并使用 Fisher 精确检验确定不育男性和生育男性之间等位基因频率的差异。不育男性的 T 和 C 等位基因频率分别为 71%和 29%，而生育男性的 T 和 C 等位基因频率分别为 80%和 20%。等位基因频率的差异具有统计学意义（p=0.002）。与其他基因型相比，CC 基因型的不育男性的精子计数和活力明显下降，死精子数量增加。
根据印度的研究，我们得出结论，CYP1A1 的 CC 基因型与男性不育的发病机制有关。
