GSTM1及GSTT1和GSTP1基因多态性对尿中1-羟基芘水平的影响

Modification of GSTM1, GSTT1 and GSTP1 gene polymorphisms on urinary 1-hydroxypyrene excretions

目的研究GSTM1、GSTT1和GSTP1基因多态性对多环芳烃接触工人尿中1．羟基芘（1．OHP）水平的影响。方法分别选取2个炼焦厂共447名多环芳烃职业接触工人（接触组）和某线材厂220名非职业接触工人（对照组）作为研究对象，采用高效液相色谱法测定尿中1-OHP水平，采用线性回归统计模型分析GSTM1和GSTT1缺失型及GSTP11105V位点的多态性对不同人群尿中1-OHP水平的修饰作用。结果接触组工人尿中1-OHP浓度为4．61μmol／molCr，明显高于对照组（0．34μmol/molCr），差异有统计学意义（P〈0．05）。接触类别和吸烟分别是影响尿中1-OHP水平的主要因素，在控制各混杂因素的影响后，线性回归分析显示，接触组尿中1-OHP水平和GSTP11105V位点多态性有关（单基因分析，P=0．012；多基因分析，P=0．011），对总体样本，单基因模型和多基因模型均显示，尿中1-OHP水平可能和GSTT1缺失型多态有关（P=0．055），多基因交互作用分析显示，GSTT1和GSTPI基因多态对接触组尿中1—OHP水平具有交互作用。结论谷胱甘肽硫转移酶（GSTs）基因的多态性对接触多环芳烃工人尿中1-OHP水平有影响。

Objective To investigate the modification of GSTM1, GSTT1 and GSTP1 gene polymorphisms on urinary 1-hydroxypyrene （1-OHP） excretions in workers under different exposure levels. Methods Four hundred and forty-seven occupationally exposed workers from two coking plants and 220 control workers from a wire rod plant were genotyped to analyze the modification of GSTM1, GSTT1 and GSTP1 gene polymorphisms on urinary 1-OHP excretions. Results The minary 1-OHP concentration in exposed group was much higher than that in control group （4.61 vs 0.34 μmol/mol Cr, P〈0.05）. Occupational exposure levels and cigarette smoking were of the dominating factors affecting 1-OHP excretions in urine. After controlling potential confounders, decreased excretion of urinary 1-OHP was associated with GSTP1 1105V AG ＋ GG genotype in coke oven workers （single-gene model, P=0.012; multi-gene model, P=0.011 ） and with GSTT1 null type in the analysis including all subjects （P=0.055 in both single-gene and multi-gene models）. GSTT1 and GSTP1 were interacted on the urinary concentrations of 1-OHP. Conclusion Urinary 1-OHP concentrations can be modified by GSTM1, GSTT1 and GSTP1 gene polymorphisms, indicating that these genes are involved in the metabolism of polycyclic aromatic hydrocarbons.