苯作业工人职业流行病学研究及MDR1基因多态性对白细胞计数的影响
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摘要
职业性苯中毒是常见的职业病之一,2002年由卫生部颁布了《职业性苯中毒诊断标准》(GBZ 68-2002),2008年对《职业性苯中毒诊断标准》(GBZ 68-2002)进行了修订,修订内容主要包括增加单纯血小板计数减少为诊断的起点指标。为探讨苯接触人群单纯血小板减少的可能机制,本研究对苯作业工人进行职业流行病学调查,设计统一问卷调查表,估算工人累计接触苯剂量,检测工人外周血血常规,采用酶联免疫吸附法检测对照组和接触组血小板相关抗体PAIgG、PAIgA、PAIgM,观察苯作业工人血小板抗体水平的变化规律。本组研究对象作业环境中苯浓度0.25～15.70mg／m3,个体累积接苯浓度1.71～74.2mg／(m3.a)。接触组PAIgG、PAIgA、PAIgM增高,PAIgA异常检出率升高,随累积接苯浓度增加,PAIgA、PAIgM有升高趋势,存在剂量-效应关系。吸烟、饮酒苯作业工人PAIg明显高于对照组,而非吸烟以及非饮酒苯作业工人PAIgG、PAIgM异常不显著。提示接触低浓度苯时,血小板相关抗体改变可能出现于外周血常规异常以前,免疫破坏是苯中毒患者单纯血小板减少的可能机制,吸烟、饮酒等因素可能起到协同作用。
为寻找一种新的苯血液毒性易感性标志物以及探讨苯血液毒性机制的新途径,本研究分别利用聚合酶链反应-限制性片段长度多态性分析和高分辨熔解曲线分析技术两种方法检测110例正常对照组和121例苯作业工人MDRl的基因多态性,并对苯作业工人中携带不同基因型个体的白细胞计数进行比较。对照组MDR1 3435 C/C基因型37.27%,C／T基因型46.36%,T／T基因型16.36%；接触组C／C基因型38.84%,C／T基因型39.67%,T／T基因型21.49%,两组差异无统计学意义(P=0.686)。接触组T／T基因型WBC 5.46±1.51×109／L,C／C+C／T基因型WBC 6.08±1.28×109／L,前者明显低于后者(P=0.044)。HRM与PCR-RFLP检测结论一致,前者比后者易于操作、价格便宜。
Benzene poisoning is a common occupational disease.《Diagnostic criteria of occupational benzene poisoning》(GBZ 68-2002) was promulgated in 2002 which was amended in 2008. Defining the platelet counts reduction as the starting point of the diagnostic criteria was the amendment description of the new diagnostic criteria. To investigate the mechanism of platelet counts reduction in benzene poisoning, we designed a unified questionnaire with occupational epidemiology method, estimated the cumulative exposure benzene doses, measured the blood routine examination and the platelet associated antibodies PAIgG、PAIgA、PAIgM with ELISA and explored the changes of platelet associated antibodies in benzene exposed workers. In this operating environment, benzene concentrations were from 0.25 to 15.70mg/m3. Cumulative exposure doses of exposed group were from 1.71 to 74.2 mg/(m3. a). The WBC、Hb、PLT of exposed workers were not significantly different from those of controls. The PAIgG、PAIgA、PAIgM and the proportion of elevated of PAIgA in exposed group were significantly higher (P<0.05) than those of the controls. PAIgA、PAIgM tended to elevate when the cumulative exposure doses of benzene were increasing in a dose-effect dependent manner. After stratification by smoking、drinking, the changes were still significant in smoking、drinking group or male, but not in non-smoking、non-drinking group or female. (P>0.05). Even though the low benzene concentration in operating environment, platelet associated antibodies may be changed before blood routine become abnormal, and smoking or drinking may interact with these changes.
In order to explore a new genetic suseptibility biomarker and a novel mechanism to hematotoxicity from benzene, PCR-RFLP and HRM were utilized to detect the polymorphism of MDR1 in 110 healthy controls and 121 workers occupationally exposed to benzene and the influence on WBC produced by this polymorphism in benzene exposed workers. The frequency of MDR1 3435 C/C, C/T, T/T in healthy controls respectively was 37.27%,46.36%,16.36%, which in wokers exposed to benzene respectively was 38.84%,39.67%,21.49%. The frequency of the MDR1 gene polymorphism was also not significantly different between benzene exposed workers and controls. Subjects exposed to benzene with MDR1 3435 mutation genotype (T/T) had the significantly lower WBC(5.46±1.51×109/L) than those carring wild type (C/C) and heterozygous (C/T), whose WBC were 6.08±1.28×109/L (P=0.044). The results analyzed respectively by HRM and PCR-RFLP were consistent, while the former was easier to operate and had the lower costs than the latter.
为寻找一种新的苯血液毒性易感性标志物以及探讨苯血液毒性机制的新途径,本研究分别利用聚合酶链反应-限制性片段长度多态性分析和高分辨熔解曲线分析技术两种方法检测110例正常对照组和121例苯作业工人MDRl的基因多态性,并对苯作业工人中携带不同基因型个体的白细胞计数进行比较。对照组MDR1 3435 C/C基因型37.27%,C／T基因型46.36%,T／T基因型16.36%；接触组C／C基因型38.84%,C／T基因型39.67%,T／T基因型21.49%,两组差异无统计学意义(P=0.686)。接触组T／T基因型WBC 5.46±1.51×109／L,C／C+C／T基因型WBC 6.08±1.28×109／L,前者明显低于后者(P=0.044)。HRM与PCR-RFLP检测结论一致,前者比后者易于操作、价格便宜。
Benzene poisoning is a common occupational disease.《Diagnostic criteria of occupational benzene poisoning》(GBZ 68-2002) was promulgated in 2002 which was amended in 2008. Defining the platelet counts reduction as the starting point of the diagnostic criteria was the amendment description of the new diagnostic criteria. To investigate the mechanism of platelet counts reduction in benzene poisoning, we designed a unified questionnaire with occupational epidemiology method, estimated the cumulative exposure benzene doses, measured the blood routine examination and the platelet associated antibodies PAIgG、PAIgA、PAIgM with ELISA and explored the changes of platelet associated antibodies in benzene exposed workers. In this operating environment, benzene concentrations were from 0.25 to 15.70mg/m3. Cumulative exposure doses of exposed group were from 1.71 to 74.2 mg/(m3. a). The WBC、Hb、PLT of exposed workers were not significantly different from those of controls. The PAIgG、PAIgA、PAIgM and the proportion of elevated of PAIgA in exposed group were significantly higher (P<0.05) than those of the controls. PAIgA、PAIgM tended to elevate when the cumulative exposure doses of benzene were increasing in a dose-effect dependent manner. After stratification by smoking、drinking, the changes were still significant in smoking、drinking group or male, but not in non-smoking、non-drinking group or female. (P>0.05). Even though the low benzene concentration in operating environment, platelet associated antibodies may be changed before blood routine become abnormal, and smoking or drinking may interact with these changes.
In order to explore a new genetic suseptibility biomarker and a novel mechanism to hematotoxicity from benzene, PCR-RFLP and HRM were utilized to detect the polymorphism of MDR1 in 110 healthy controls and 121 workers occupationally exposed to benzene and the influence on WBC produced by this polymorphism in benzene exposed workers. The frequency of MDR1 3435 C/C, C/T, T/T in healthy controls respectively was 37.27%,46.36%,16.36%, which in wokers exposed to benzene respectively was 38.84%,39.67%,21.49%. The frequency of the MDR1 gene polymorphism was also not significantly different between benzene exposed workers and controls. Subjects exposed to benzene with MDR1 3435 mutation genotype (T/T) had the significantly lower WBC(5.46±1.51×109/L) than those carring wild type (C/C) and heterozygous (C/T), whose WBC were 6.08±1.28×109/L (P=0.044). The results analyzed respectively by HRM and PCR-RFLP were consistent, while the former was easier to operate and had the lower costs than the latter.
引文
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