Zhang Y, Liu Q, Liu Q, Duan H, Cheng J, Jiang S, Huang X, Leng S, He F, Zheng Y
National Institute for Occupational Health and Poison Control, Chinese Centre for Disease Control and Prevention, Beijing, China.
Biomarkers. 2006 Jan-Feb;11(1):61-9. doi: 10.1080/13547500500451176.
Chronic exposure to n-hexane may result in peripheral neuropathy. 2,5-Hexanedione (2,5-HD) has been identified as a toxic metabolite of n-hexane. The CYP2E1, CYP1A1 and GST genes are involved in the formation of 2,5-hexanedione from n-hexane as well as the elimination of 2,5-HD-formed electrophile, and these genes are highly polymorphic in the general population. A nested case-control study in an industrial cohort was conducted to evaluate the associations between polymorphisms in these metabolic genes and n-hexane-induced peripheral nerve damage. The study subjects included 22 cases, who worked in a printing factory with symptoms of peripheral nerve damage, and 163 controls, who came from the same factory of cases. DNA was extracted from blood samples and genotyping was conducted for CYP2E1 Pst, CYP2E1 Dra, CYP2E1 Ins96, CYP1A1 Msp, GSTT1 null, GSTM1 null and GSTP1 105V. Unconditional logistic regression was applied to estimate the odds ratio and 95% confidence intervals. There were no significant differences between the two groups regarding age, sex, smoking and alcohol status. A significant association between Dra polymorphism and peripheral nerve damage was found. The frequency of CYP2E1 Dra homozygous mutation in the case group (18.2%) was higher than that in the control group (3.7%, p=0.015). Individuals with homozygote genotype (CC) of CYP2E1 Dra had a significantly higher risk of peripheral nerve damage compared with those with DD genotype (adjusted OR=?.58, 95% CI=1.32-23.65) after n-hexane exposure duration, sex, age, smoking and alcohol status were adjusted. No significant association was found that CYP2E1 Pst, CYP2E1 Ins96, CYP1A1 Msp, GSTT1, GSTM1, GSTP gene polymorphisms associated with the susceptibility of peripheral nerve damage. These findings suggested that CYP2E1 gene might increase the susceptibility to n-hexane-induced peripheral damage.
长期接触正己烷可能导致周围神经病变。2,5 - 己二酮（2,5 - HD）已被确认为正己烷的一种有毒代谢产物。细胞色素P450 2E1（CYP2E1）、细胞色素P450 1A1（CYP1A1）和谷胱甘肽S - 转移酶（GST）基因参与了正己烷形成2,5 - 己二酮的过程以及2,5 - HD形成的亲电试剂的消除过程，并且这些基因在普通人群中具有高度多态性。在一个工业队列中进行了一项巢式病例对照研究，以评估这些代谢基因多态性与正己烷诱导的周围神经损伤之间的关联。研究对象包括22例在印刷厂工作且有周围神经损伤症状的病例，以及163例来自与病例同一工厂的对照。从血液样本中提取DNA，并对CYP2E1 Pst、CYP2E1 Dra、CYP2E1 Ins96、CYP1A1 Msp、GSTT1缺失、GSTM1缺失和GSTP1 105V进行基因分型。应用无条件逻辑回归来估计比值比和95%置信区间。两组在年龄、性别、吸烟和饮酒状况方面无显著差异。发现Dra多态性与周围神经损伤之间存在显著关联。病例组中CYP2E1 Dra纯合突变的频率（18.2%）高于对照组（3.7%，p = 0.015）。在调整了正己烷暴露时间、性别、年龄、吸烟和饮酒状况后，CYP2E1 Dra纯合子基因型（CC）个体相比DD基因型个体，周围神经损伤风险显著更高（调整后的比值比 = ？.58，95%置信区间 = 1.32 - 23.65）。未发现CYP2E1 Pst、CYP2E1 Ins96、CYP1A1 Msp、GSTT1、GSTM1、GSTP基因多态性与周围神经损伤易感性之间存在显著关联。这些发现表明CYP2E1基因可能会增加对正己烷诱导的周围损伤的易感性。
