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细胞色素P450 1A1和2D6基因多态性与慢性苯中毒的危险性

Genetic polymorphism of CYP1A1,CYP2D6 and risks of chronic benzene poisoning

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【作者】 顾寿永张忠彬曹多志万俊香高晓玲金锡鹏夏昭林

【Author】 GU Shouyong ZHANG Zhongbin, CAO Duozhi, WAN Junxiang, GAO Xiaoling, JIN Xipeng,XIA Zhaolin .Department of Occupational Health, School of Public Health, Fudan University, Shanghai 200032, China

【机构】 复旦大学公共卫生学院劳动卫生教研室马鞍山钢铁公司医院劳动卫生研究所上海市第一人民医院

【摘要】 [目的]探讨探讨细胞色素P450 1A1利2D6基因多态性与慢性苯中毒易感性的关系。[方法]采用病例一对照研究,选择152名苯中毒工人为病例组,152名接触苯而无中毒表现的工人为对照组。采用PCR-RFLP技术检测CYP1A1基因3’端非编码区Msp I和CYP2D6第1外显子c.188位点、g.212位点多态性。[结果]携带CYP1A1 Msp□T/T基因型的个体发生苯中毒的危险性是携带有CYP1A1Msp□T/C或C/C基因型的个体的1.32倍(95%CI 1.05-1.65,P=0.02):在不吸烟的人群中,携带CYP1A1Msp□T/T基因型的个体发生苯中毒的风险性是携带T/C或C/C基因型的个体的1.56倍(95%CI:1.15-2.12,P=0.003);携带有CYP2D6 c.188 C/C或C/T基因型个体发生苯中毒的危险性是携带有CYP2D6c.188T/T基因型的个体的1.23倍(95%CI:1.05-1.42,P=0.01),在不吸烟的人群中,携带CYP2D6c.188 C/C或C/T基因型个体发生苯中毒的危险性是携带有CYP2D6 c.188T/T基因型的个体的1.23倍(95%CI:1.04-1.47,P=0.01)。未发现研究对象的CYP2D6g.212位点存在多态性。[结论]携带CYP1A1 Msp□T/T基因型、CYP2D6 C.188 C/C和C/T基因型个体对苯中毒可能易感

【Abstract】 [Objective] To explore the association of genetic polymorphisms of CYP 1A1 and CYP2D6 with risks of chronic benzene poisoning (BP). [Methods] A case-control study was conducted. 152 BP patients and 152 workers occupationally exposed to benzene without poisoning manifestations were involved. Polymerase chain reaction followed by restriction fragment length polymorphism (PCR-RFLP) technology were used to detect the single nucleotide polymorphisms (SNPs)of Msp I in the non-coding region of CYP 1A1 gene and c. 188,g.212 position in the first extron of CYP2D6 gene. [Results] The individuals with CYP1A1 Msp I T/T genotype had a 1.32-fold (95%CI: 1.05-1.65, P=0.02) increased risk of BP compared with those carrying T/C and C/C genotypes. In no-smoking population, there was a 1.56-fold (95%CI: 1.15-2.12, P=0.003) increased risk of BP for subjects carrying CYP1A1 Msp I T/T genotype compared with those carrying T/C and C/C genotypes. The individuals carrying CYP2D6c.188 C/C or C/T genotype had a 1.23-fold (95%CI: 1.05-1.42,P=0.01) increased risk compared with those carrying T/T genotypes. In no-smoking population, there was a 1.23-fold (95%CI: 1.04-1.47, P=0.01) increased risk of BP for subjects carrying CYP2D6c.188 C/C or C/T genotypes compared with those carrying T/T genotype. The single nucleotide polymorphism of g.212 position in the first extron of CYP2D6 gene has not been validated. [Conclusion] It was suggested that the individuals with CYP2D6 c.188 C/C, CYP2D6 c.188 C/T and CYP1A1 Msp /T/T genotypes tended to be more susceptible to benzene toxicity.

【基金】 国家自然科学基金项目(30271113);国家科技部973项目(2002CB512902)
  • 【会议录名称】 第四届全国环境与职业医学研究生学术研讨会论文集
  • 【会议名称】第四届全国环境与职业医学研究生学术研讨会
  • 【会议时间】2005-04
  • 【会议地点】中国南京
  • 【分类号】R135
  • 【主办单位】《环境与职业医学》杂志、东南大学公共卫生学院、环境与职业医学研究生研究会
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