热休克蛋白B1基因、肿瘤抑制蛋白p53基因多态性与焦炉作业工人染色体损伤的关联及其交互作用分析  

Association and interaction of heat shock proteins B1 gene and tumor-suppressor protein p53 gene ;with chromosome damage levels among coke oven workers

作　　者：李晓亮[1,2] 邓棋霏[1] 张笑[1] 王甜[1] 陈卓旺 白岩森 王素菡[1] 邬堂春[1] 郭欢[1] 

机构地区：[1]华中科技大学同济医学院公共卫生学院劳动卫生与环境卫生学系环境与健康教育部重点实验室,武汉430030 [2]珠海市慢性病防治中心职业卫生科

出　　处：《中华预防医学杂志》2016年第10期900-906,共7页Chinese Journal of Preventive Medicine

基　　金：国家自然科学基金（81102102、81272589）;教育部新世纪优秀人才支持计划（NCET-12-0209）;高等学校博士学科点专项科研基金（20110142120026）

摘　　要：目的：探讨热休克蛋白B1基因（HSPB1）启动子区多态性位点rs2868371和肿瘤抑制蛋白P53基因（TP53）基因多态性位点rs1042522与焦炉作业工人染色体损伤的关联及其交互作用。方法于2010年9—10月，选取武汉市某焦化厂1333名男性焦化厂工人作为调查对象，以其中在辅助车间、炉底、炉侧和炉顶等场所工作的工人作为暴露组，共949名；在办公室场所工作的行政、医务人员作为对照组，共384名。收集调查对象的人口学信息并采集外周静脉血5 ml，分别运用ELISA和胞质分裂阻滞试验测定其血浆苯并[a]芘二氢二醇环氧化物-白蛋白（BPDE-白蛋白）加合物的浓度和外周血淋巴细胞微核率，采用TaqMan探针技术和ABI Prism 7900HT型荧光定量PCR仪进行SNP分型检测，并计算频率比（FR）及其95%CI值。结果暴露组中，携带rs2868371 GG基因型者外周血淋巴细胞微核率为（3.52±2.67）‰，均低于携带GC、CC及GC＋CC基因型者[分别为（3.88±2.88）‰、（4.00±2.66）‰和（3.91±2.83）‰]（FR值分别为1.10、1.13、1.11，95%CI值分别为1.02~1.19、1.02~1.25、1.03~1.19），且rs2868371 C有明显的等位基因剂量-效应关系（P趋势=0.006）；携带rs1042522 CC基因型者微核率为（3.95±3.06）‰，均高于携带CG以及CG＋GG基因型者[分别为（3.63±2.61）‰、（3.66±2.61）‰]（FR值分别为0.87、0.90，95%CI值分别为0.83~0.96、0.84~0.97）。HSPB1 rs2868371和TP53 rs1042522对外周血淋巴细胞微核率水平存在交互作用（P交互=0.001）。年龄〉40岁（FR=1.07，95%CI：1.01~1.12）、工龄〉20年（FR=1.08，95%CI：1.02~1.14）、BMI≤24 kg/m2（FR=1.07，95%CI：1.01~1.13）、饮酒（FR=1.09，95%CI：1.02~1.16）以及高BPDE-白蛋白水平（FR=1.07，95%CI：1.01~1.13）者HSPB1 rs2868371 C等位基因与微核率的增加均具有等位基因剂量-效应关系（P趋势分别为0.023、0.013、0.029和0.020）；年龄〉40岁（FR=0.94Objective To investigate the association and interaction of heat shock proteins B1 （HSPB1） gene rs2868371 and tumor-suppressor protein p53 （TP53） gene rs1042522 polymorphisms with chromosome damage levels among coke oven workers. Methods We recruited 1 333 male workers from a state-run coke oven plant in Wuhan in September-October 2010. Among them, 949 who had worked in coke oven workplaces, including auxiliary facilities and bottom, side, and top ovens, were nominated as coke oven workers （i.e., exposed）, and 384 administrative or medical staff whose workplaces were offices were used as controls. General characteristics and 5 ml of venous blood were collected from each participant. The plasma concentrations of benzo [a] pyrene-diolepoxide （BPDE）-albumin adducts and the lymphocytic micronucleus （MN） frequencies for each individual were detected by ELISA and cytokinesis-block micronucleus assay, respectively. Gene polymorphisms were genotyped using TaqMan assays via quantitative PCR （ABI Prism 7900HT）, and the corresponding frequency ratios （FR） with 95%confidence intervals （CI） were computed for all assays. Results In the exposed group, the MN frequencies were higher in HSPB1 rs2868371 GC, CC, and GC＋CC genotype carriers （（3.88 ± 2.88）‰, （4.00 ± 2.66）‰, and （3.91 ± 2.83）‰, respectively） than in rs2868371 GG genotype carriers （（3.52±2.67）‰;FR=1.10, 1.13, and 1.11;95%CI：1.02-1.19, 1.02-1.25, and 1.03-1.19, respectively）, and the HSPB1 rs2868371C allele was associated with increased MN frequency （Ptrend=0.006）. Further, in the exposed group, the MN frequencies were lower in TP53 rs1042522 CG and CG＋GG genotype carriers （（3.63±2.61）‰and （3.66±2.61）‰, respectively） than in TP53 rs1042522 CC genotype carriers （3.95 ± 3.06）‰（FR=0.87 and 0.90;95%CI：0.83-0.96 and 0.84-0.97, respectively）. The effect of gene-gene interaction between HSPB1, rs2868371, and TP53 rs1042522 on MN frequency was significant among coke oven

关 键 词：多态性 单核苷酸 HSP27热休克蛋白 肿瘤抑制蛋白质P53 焦炉工 Tumor suppressor protein p53 

分 类 号：R135[医药卫生—劳动卫生]