ALDH2、CYP1A1和CYP2E1基因多态性及吸烟和饮酒习惯对人体甲苯代谢的影响
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川本T，古贺M，村田K，松田S，小玉Y
ALDH2、CYP1A1和CYP2E1基因多态性及吸烟和饮酒习惯对人体甲苯代谢的影响
中国药理学杂志，1995年8月;133(2):295-304。
- PubMed ID
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7645026 (PubMed视图］
- 摘要
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在本研究中，我们评估了ALDH2、CYP1A1和CYP2E1基因多态性以及吸烟和饮酒习惯对甲苯代谢的影响。研究对象是在日本印刷厂、电器零件厂、油漆厂工作的92名处理甲苯的男性。使用扩散式采样器监测他们对甲苯的暴露水平。在工作结束时测定了他们血液中的苯甲醇浓度和hippuric acid (HA)以及尿液中的肌酐浓度。ALDH2基因型分为正常ALDH2基因纯合型(NN)、失活ALDH2基因纯合型(DD)和正常与失活ALDH2基因杂合型(ND)。采用限制性片段长度多态性(RFLP)检测CYP1A1和CYP2E1的遗传多态性。观察到个人暴露水平与尿中HA浓度之间有很强的相关性。将ALDH2、CYP1A1、CYP2E1、吸烟、饮酒5个因素除以，计算回归线。ALDH2基因型间甲苯HA形成差异显著(p < 0.001)。回归线的斜率从NN到ND再到DD依次递减。 The benzyl alcohol concentration in the blood of the DD group was significantly higher than that found in the NN and ND groups. This result demonstrates that ALDH2 polymorphism affects the oxidation of benzyl alcohol to benzoic acid. The toluene metabolism was also affected by CYP1A1 polymorphism. The slope for the Ile/Ile (the predominant homozygous allele) group was significantly lower than that for the Ile/Val (the heterozygous allele) and Val/Val (the rare homozygous allele) group after correction for creatinine. A drinking habit significantly (p < 0.05) reduced urinary HA concentration in the NN group. A smoking habit also significantly (p < 0.05) reduced urinary uncorrected HA concentration in both the NN and ND groups. In a multiple regression analysis, ALDH2 and the drinking habit were significantly (p < 0.01) associated with HA excretion after toluene exposure with and without correction for creatinine, and the corrected HA concentration was also significantly (p < 0.01) increased in the Ile/Val and Val/Val group of CYP1A1. The smoking habit reduced the corrected HA concentration (p < 0.05); however, the polymorphism in the 5'-flanking region of CYP2E1 did not affect HA appearance in urine.