Polymorphism of a gene that metabolize chemical substance, biological monitoring and health effect

细胞原体P450 2E1 （CYP2E1）参与化学物质代谢。CYP2E1启动子区域具有多态性，即基因型为1/1、1/2和2/2。按照这个顺序，表达水平会变得更高。在本研究中，我们通过研究经皮肤吸收的对肝脏有毒性的二甲基甲酰胺（DMF）来研究CYP2E1基因型与代谢或健康影响的关系。11名志愿者暴露于DMF，并检测DMF代谢物n-单甲酰胺（NMF）的生物半衰期（BHL）。DMF经皮肤吸收后BHL逐渐降低(1/1型为4.7±1.4 h (n=7)， 1/2型为3.9±0.5 h （n=3)， 2/2型为3.1 h (n=1)）。但是，由于样本量小，很难得出结论性的结论。我们让两个新的半型志愿者接触DMF。包括两名新志愿者的结果在内的分析正在进行中。二甲基乙酰胺（DMAc）也被CYP2E1代谢。因为我们有志愿者接触DMAc的实验数据，所以我们检查了志愿者的基因型。我们没有分析CYP2E1基因型与DMAc代谢的关系，因为所有的志愿者都是1/1型。健康影响横断面研究是在人们接触DMF的工厂进行的。我们计划检查两件事。1) dmf对健康有不良影响吗？2)如果观察到不良健康影响，CYP2E1基因型是否会影响结果？特别注意肝脏或神经元功能（中枢和周围神经系统）。主观症状或客观检查如临床化学等部分项目初步呈阳性，但调整混杂因素后未见正相关。在我们研究的工厂中，没有观察到明显的不良健康影响。因此，不受CYP2E1的修饰

Cytocrome P450 2E1 (CYP2E1) is enrolled to metabolism of chemical substances. Promoter region of CYP2E1 is polymorphic, namely genotype 1/1, 1/2 and 2/2. Expression level becomes higher in that order. In this study, we investigated relationship between CYP2E1 genotype and metabolism or health effect through the study of dimethylformamide (DMF), which is toxic to liver, absorbed through Skin.Metabolism Eleven volunteers were exposed to DMF and the biological half-life (BHL) of n-monomthylformamide (NMF), which is the metabolite of DMF, was examined. Especially when DMF was absorbed through skin, BHL showed stepwise decrease (4.7±1.4 hours for 1/1 type (n=7), 3.9±0.5 hours for 1/2 type (n=3) and 3.1 hours for 2/2 type (n=1)). But, it was difficult to say conclusive thing for its small sample size. We exposed two new 1/2 type volunteers to DMF. Analysis including the result of two new volunteer is now under way.Dimethylacetoamide (DMAc) is also metabolized by CYP2E1. Because we have the volunteer exposure experiment data of DMAc, we examined the genotype of volunteers. We failed to analize the relationship of CYP2E1 genotype and DMAc metabolism, because all of volunteers was 1/1 type.Health effect Cross-sectional study was done in the factory where people handle with DMF. We planned to examine two things. 1) Is there any adverse health effect due toDMF? 2) Does genotype of CYP2E1 affect the result, if we observed adverse health effect? Attention was specially paid to hepatic or neuronal function (both central and peripheral nervous system). Some items on subjective symptom or objective examination such as clinical chemistry showed tentative positive result, but we could not observe positive relationship after adjustment of confounding factors. In the factory we studied, no clear-cut adverse health effect was observed. Therefore, no modification by CYP2E1