目的探讨环氧化物水解酶1(epoxidehydrolase1,EPHXl)基因多态性对苯乙烯体内代谢的影响。方法选择山东省某玻璃钢游艇生产企业喷漆车间工龄在1年以上,防护情况基本相同的全部工人(56人)作为研究对象。分别测定个体苯乙烯8h时间加权平均浓度(8h-TWA)、尿中代谢产物一苯乙醇酸(mandelicacid,MA)和苯乙醛酸(phenylglyoxylicacid,PGA)浓度,采用聚合酶链反应一限制性片段长度多态性(PCR—RFLP)法检测研究对象的EPHXl基因多态性。结果工人尿中MA浓度为(177.25±82.36)mg/gCr,PGA浓度为(145.91±69.73)mg/gCr,苯乙烯8h—TWA为(133.28±95.81)mg/m3。尿中MA及PGA浓度与苯乙烯8h—TWA均呈正相关关系(R:0.861,P〈0.05;R=0.868,P〈0.05)。按苯乙烯8h-TWA〉50mg/m。为高暴露组,8h-‘1wA≤50mg/m,为低暴露组,将研究对象分为高暴露组和低暴露组,高暴露组和低暴露组受试者携带高活力EPHXI基因型个体尿中的MA和PGA浓度明显高于携带EPHXl低活力组基因型者,差异有统计学意义(P《0.05)。结论EPHXI基因多态性对苯乙烯在体内的代谢过程可能有一定影响。
Objective To investigate the role of genetic polymorphisms of epoxide hydrolase 1 (EPHX1) in the metabolism of styrene in vivo. Methods Fifty-six styrene-exposed workers, who worked in the painting workshop of an enterprise for manufacturing glass fiber-reinforced plastic yachts in Shandong Province, China for over one year and were protected in approximately the same way, were selected as study subjects. The 8-hour time-weighted average concentration (8 h-TWA) of styrene and the concentrations of mandelic acid (MA) and phenyl glyoxylic acid (PGA) as urinary metabolites were measured. The genetic polymorphisms of EPHX1 were detected by polymerase chain reaction-restriction fragment length polymorphism analysis. Results The urinary concentrations of MA and PGA were 177.25+82.36 mg/g Cr and 145.91+69.73 mg/g Cr, respective- ly, and the 8 h-TWA of styrene was 133.28+95.81 mg/m3. Urinary concentrations of MA and PGA were posi- tively correlated with 8 h-TWA of styrene (R =0.861, P〈0.05; R=0.868, P〈0.05). The subjects were divided into high-exposure group (8 h-TWA 〉50 mg/m3) and low-exposure group (8 h-TWA ~〈 50 rag/m3), and in the two groups, the urinary concentrations of MA and PGA were significantly higher in the individuals carrying high-ac- tivity genotypes of EPHXI than in those carrying low-activity genotypes of EPHX1 (P〈0.05). Conclusion Genetic polymorphisms of EPHX 1 play an important role in the metabolic process of styrene in vivo.