目的 研究CYP1A1多态性与焦炉工尿中1-羟基芘水平的关系。方法 按照苯并pa]芘(B[a]P)接触水平将223名焦炉工分为炉顶组(76名)、炉侧组(82名)和炉底组(65名),以119名无职业性接触多环芳烃的工人为对照组,采用聚合酶链反应-限制性片段长度多态性分析(PCR—RFLP)CYP1A1基因MspI位点多态性、等位基因特异性扩增方法检测CYP1A1基因1462V位点的多态性。结果 炉顶组、炉侧组和炉底组焦炉工尿中1-羟基芘水平分别为(3.77±0.64)、(3.57±0.49)、(3.26±0.80)μmol/mol Cr,明显高于对照组,差异有统计学意义(P〈0.01)。各组CYP1A1 MspI位点各基因型的尿中1-羟基芘水平差异均无统计学意义(P〉0.05)。炉侧组和炉顶组CYP1A1 1462V位点的各基因型尿中1-羟基芘水平均为Ⅱe/Ⅱe〈Ⅱe/Val〈Val,Val,差异有统计学意义(P〈0.01)。多元直线回归分析表明,尿中1-羟基芘水平主要受B[a]P接触水平和CYP1A1 1462V位点基因型的影响;logistic回归分析表明,炉顶组、炉侧组和炉底组尿中1-羟基芘增高的OR值分别为对照组的24.926、6.729和4.226倍,CYP1A1 MspI位点m2/m2和ml/m2基因型尿中1-羟基芘增高的OR值分别为ml/ml基因型的4.031和1.794倍,Val/Val和Ile/Val基因型尿1-羟基芘增高的OR值分别为Ile/ile基因型的5.524和3.811倍。结论 焦炉工尿1-羟基芘水平与工作环境中苯并[a]芘暴露趋势一致,CYP1A1 MspI位点和1462V位点基因多态性影响焦炉工尿中1-羟基芘的水平。
Objective To study the associations of CYP1A1 gene polymorphisms with levels of urinary 1-hydroxypyrene among coke oven workers. Methods 223 male workers from a coke plant (76, 82 and 65 workers in oven top group ,oven-side group and oven-bottom group respectively) and 119 controls without occupational polycyclic aromatic hydrocarbons exposure were selected. The MspI gene polymorphism in CYP1A1 3'flanking region and the genotypes at I462V site in exon 7 of CYP1A1 were detected by polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP) and allele specific amplification (ASA). Results The urinary 1-hydroxypyrene of coke oven workers in oven-top,oven-side and oven-bottom(3.77±0.64,3.57±0.49,3.26±0.80 μmol/mol Cr) were significantly higher than controls(2.80±1.02 μmol/mol Cr)(P〈0.01). The urinary 1-hydroxypyrene was not significantly different among MspI genotypes in CYP1A1 3 'flanking region (P〉0.05). In oven-top group and oven-side group,the subjects with Val/ Val genotype in exon 7 of CYP1A1 had significantly higher urinary 1-hydroxypyrene levels than those with Ile/Val or Ile/Ile genotype,and urinary 1-hydroxypyrene of Ile-Val genotype were also significantly higher than Ile/Ile genotype (P〈0.01). Multivariate logistic regression analysis showed that the coke oven workers (OR in oven top group,oven-side group and oven-bottom group was 24.926,4.226 and 6.729 respectively) and subjects with m2/m2 genotype in CYP1A1 3'flanking region (OR=4.031) or with Val/Val or Ile/Val genotype in exon 7 of CYPIA1 (OR were 5.524 and 3.811 ) had elevated urinary 1-hydroxypyrene (greater than 95 percentile of control group,3.876 μmol/mol Cr). Conclusion BAP concentration of work environment contributes to the elevated urinary 1-hydroxypyrene levels, and the exposed BAP levels were regnlated by the CYP1A1 MspI and I462V genotypes. Genetic polymorphism of CYP1A1 gene could be a susceptible biomarker in coke oven workers which was involved in the in