Young Chi-Hsien, Lo Yu-Lun, Tsai Yi-Yu, Shih Tung-Sheng, Lee Huei, Cheng Ya-Wen
Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan.
Mol Vis. 2010 Jun 9;16:1054-8.
Both cytochrome P4501A1 (CYP1A1) and glutathione S-transferase M1 (GSTM1) have been demonstrated to be involved in the metabolism of polycyclic aromatic hydrocarbons (PAHs). BaP 7,8-diol 9,10-epoxide (BPDE), an ultimate metabolite of benzo(a)pyrene (BaP), attacks deoxyguanosine to form a BPDE-N2-dG adduct resulting in p53 gene mutations. Our previous report indicated that BPDE-like DNA adduct levels in pterygium were associated with CYP1A1 gene polymorphisms. Therefore, we hypothesize that the genetic polymorphisms of CYP1A1 and GSTM1 increase the risk for pterygium.
Two hundred-five pterygial specimens and 206 normal controls were collected in this study. For the analysis of CYP1A1 and GSTM1 gene polymorphisms, DNA samples were extracted from blood cells and then subjected to restriction fragment length polymorphism and polymerase chain reaction for the determination of mutation and genotype of CYP1A1 and GSTM1.
There was a significant difference between the case and control groups in the CYP1A1 genotype (p=0.0161) but not in GSTM1 (p=1.000). The odds ratio of the CYP1A1 m1/m2 polymorphism was 1.327 (95% CI=0.906-2.079, p=0.135) and the m2/m2 polymorphism was 1.647 (95% CI=1.154-2.350, p=0.006), compared to the m1/m1 wild-type genotype. The GSTM1 polymorphisms did not have an increased odds ratio compared with the wild type.
In conclusion, a CYP1A1 polymorphism is correlated with pterygium and might become a marker for the prediction of pterygium susceptibility.
细胞色素P4501A1(CYP1A1)和谷胱甘肽S-转移酶M1(GSTM1)均已被证明参与多环芳烃(PAHs)的代谢。苯并(a)芘(BaP)的终末代谢产物BaP 7,8-二醇9,10-环氧化物(BPDE)会攻击脱氧鸟苷,形成BPDE-N2-dG加合物,从而导致p53基因突变。我们之前的报告表明,翼状胬肉中类似BPDE的DNA加合物水平与CYP1A1基因多态性有关。因此,我们推测CYP1A1和GSTM1的基因多态性会增加翼状胬肉的发病风险。
本研究收集了205份翼状胬肉标本和206份正常对照。为分析CYP1A1和GSTM1基因多态性,从血细胞中提取DNA样本,然后进行限制性片段长度多态性分析和聚合酶链反应,以确定CYP1A1和GSTM1的突变和基因型。
CYP1A1基因型在病例组和对照组之间存在显著差异(p = 0.0161),而GSTM1基因型则无显著差异(p = 1.000)。与m1/m1野生型基因型相比,CYP1A1 m1/m2多态性的比值比为1.327(95%可信区间=0.906 - 2.079,p = 0.135),m2/m2多态性的比值比为1.647(95%可信区间=1.154 - 2.350,p = 0.006)。与野生型相比,GSTM1多态性的比值比并未增加。
总之,CYP1A1多态性与翼状胬肉相关,可能成为预测翼状胬肉易感性的一个标志物。