CYP286与CYP2D6和GSTP1基因多态性与苯乙烯代谢的关系

Association between CYP2B6, CYP2D6, GSTP1 genetic polymorphisms and urinary styrene metabolites in professional workers

目的探讨代谢酶基因多态性与苯乙烯接触工人尿中代谢产物的关系。方法选择58名职业接触苯乙烯工人为研究对象，根据个体接触剂量分为高接触组（≥100mg／m^3）32名和低接触组（〈100mg／m^3）26名，用微流控芯片检测方法，检测CYP286（exon4，G516T）、CYP2D6（exon1，C188T）和GSTP1（exon5，A105G）位点的多态性，分析3种代谢酶基因多态性对苯乙烯代谢的影响。结果3种基因的基因型分布符合Hardy—Weinberg平衡。高接触组携带CYP286（exon 4，G516T）GG基因型的个体尿中苯乙醇酸（MA）、苯乙醛酸（PGA）、苯乙烯巯基尿酸（PHEMA）浓度分别为（280．28±100．60）、（233．04±77．56）、（32．88±7．14）mg／g肌酐，明显高于GT＋TT基因型个体[分别为（183．48±127．52）、（152．46±95．47）、（24．47±5．59）mg／g肌酐]，差异均有统计学意义（P〈0．05）；高、低接触组GSTP1（exon 5，A105G）AA野生型尿中PHEMA浓度分别为（32．07±7．32）、（7．77±5．28）mg／g肌酐，均明显高于AG＋GG型，差异有统计学意义（P〈0．05）；高接触组CYP2D6（exon 1，C188T）CT＋TT基因型MA、PGA、PHEMA浓度高于CC基因型，差异均有统计学意义（P〈0．05）。结论CYP286、GSTP1和CYP2D6基因多态性可影响苯乙烯在人体内的代谢。

Objective To evaluate the influence of individual genetic polymorphisms of metabolic enzymes on urinary styrene metabolites. Methods 58 workers occupationally exposed to styrene were divided into the high exposure group （≥100 mg/m^3） and the low exposure group （〈100 mg/m^3）. The microfluidic chip technology was used to determine the SNPs of CYP2B6 ,CYP2D6 and GSTP1 and the influence of gene polymorphisms on the metabolism of styrene was statistically analyzed. Results The level of urine styrene metabolites level was influenced by genotypes of CYP2B6,CYP2D6 and GSTP1 [（280.28±100.60） mg/g Cr vs （183.48±127.52） mg/g Cr, （233.04±77.56） mg/g Cr vs （152.46±95.47） mg/g Cr, （32.88±7.14） mg/g Cr vs （24.47±5.59） mg/g Cr, P〈0.05）]. The metabolism of CYP2B6 G/G homozygotic genotype to styrene was more active than G/T heterozygotic genotype and T/T mutation genotype. The level of PHEMA in GSTP1 homozygotic genotype subjects was significantly higher than that in the group of homozygotie genotype [ （32.07±7.32） mg/g Cr vs （25.59±6.95） mg/g Cr,P〈0.05 ）]. The influence of CYP2D6 genotypes on urinary metabolites was also observed in the same study[（56.36±109.72） mg/g Cr vs （177.13±116.21 ） mg/g Cr, （ 118.73±84.55 ） mg/g Cr vs （148.48±99.83） mg/gCr,（18.29±13.50） mg/gCrvs （19.95±13.30） mg/gCr, P〈0.05）]. Conclusion Genotypes of CYP2B6, GSTP 1 and CYP2D6 are related to susceptibility to the metabolism of styrene in human.