中国科学院心理健康重点实验室知识库

目的评价铬酸盐职业接触对机体遗传损伤的影响,分析8-羟基鸟嘌呤DNA糖苷酶(hOGG1)基因多态性与铬酸盐致遗传损伤的关联。方法采用判断抽样方法,以136名铬酸盐作业工人为接触组,以156名无铬酸盐及其他职业病危害因素接触人员为对照组,采用电感耦合等离子体-质谱法测定2组人群周围血全血铬水平,以酶联免疫吸附试验测定尿8-羟基-脱氧鸟苷(8-OHdG)水平,采用基质辅助激光解析电离飞行时间质谱法对hOGG1基因4个单核苷酸多态性位点进行分型检测。结果接触组人群全血铬和尿8-OHdG水平均高于对照组(中位数:3.41 vs 0.90μg/L,6.02 vs 4.72μg/g肌酐,P<0.01)。对于研究对象(接触组和对照组人群),校正年龄、体质指数、性别、吸烟、饮酒等混杂因素后,铬酸盐接触可能为尿8-OHdG水平升高的危险因素(P<0.05);隐性模型下hOGG1的rs293796和rs13096551均为尿8-OHdG水平升高的危险因素(P<0.05)。对于接触组人群,校正年龄、体质指数、性别、吸烟、饮酒等混杂因素后,hOGG1的rs293796加性模型、隐性模型和rs13096551隐性模型均为尿8-OHdG水平升高的危险因素(P<0.05),rs3219008显性模型为尿8-OHdG水平升高的保护因素(P<0.05);但经Bonferroni多重检验校正后,仅rs293796隐性模型仍为接触组人群尿8-OHdG水平升高的危险因素(P<0.001),且与铬酸盐接触存在有统计学意义的交互作用(P

Abstract: Objective To evaluate the genetic damage induced by occupational chromate exposure，and to analyze the association between human 8-oxoguanine-DNA N-glycosylase 1 ( hOGG1) polymorphisms and genetic damage in population with chromate exposure． Methods A total of 136 chromate exposed workers were recruited as exposure group by judgmental sampling method，and 156 workers without chromate and other occupational hazard factors exposure were recruited as control group． The whole blood chromium ( WB-Cr) level was measured by inductively coupled plasma mass spectrometry． Urinary 8-hydroxy-2'-deoxyguanosine ( 8-OHdG) was determined by enzyme-linked immunosorbent assay．Four single nucleotide polymorphisms of hOGG1 gene were genotyped by the matrix assisted laser desorption ionization /time of flight mass spectrometry． Results The WB-Cr level was higher in the exposure group than that in the control group ( meclian: 3. 41 vs 0. 90 μg /L，P ＜ 0. 01) ． The urinary 8-OHdG level was higher in the exposure group compared with that in the control group ( meclian: 6. 02 vs 4. 72 μg /g•creatinine，P ＜ 0. 01) ． In study subjects ( exposure group and control group) ，after adjusting the potential influencing factors such as age，body mass index ( BMI) ，gender，smoking and drinking，chromate exposure might be a risk factor for increasing urinary 8-OHdG level ( P ＜ 0. 05) ，and the recessive models of rs293796 and rs13096551 were observed as risk factors of increasing urinary 8-OHdG level ( P ＜ 0. 05) ． In chromate exposure group，the additive and recessive models of rs293796 and the recessive model of rs13096551 were observed as risk factors of increasing urinary 8-OHdG level ( P £¼ 0. 05) £¬while the dominant model of rs3219008 was protective factor of increasing urinary 8-OHdG level ( P £¼ 0. 05) £¬after adjusting the potential influencing factors such as age£¬BMI£¬gender£¬smoking£¬drinking£® However£¬after multiple Bonferroni correction tests£¬only the recessive model of rs293796 was the risk factor of increasing urinary 8-OHdG level in the exposed group ( P £¼ 0. 01) £® There was significant interaction between chromate exposure and rs293796 on urinary 8-OHdG ( P £¼ 0. 01) £® Conclusion The rs13096551 and rs293796 of hOGG1 were associated with the alteration of urinary 8-OHdG level induced by chromate£® There was interaction between rs294796 of hOGG1 and chromate exposure on urinary 8-OHdG level£®

国家自然科学基金(81573118);; 北京大学医学部优秀博士创新基金