细胞色素CYP1A1基因多态与慢性苯中毒遗传易感性  

Association of Genetic Polymorphism in CYP1A1 with Susceptibility of Chronic Benzene Poisoning

作　　者：孙品[1] 张忠彬[1] 吴芬[1] 万俊香[1] 金锡鹏[1] 夏昭林[1] 

机构地区：[1]复旦大学公共卫生学院,上海200032

出　　处：《工业卫生与职业病》2007年第4期197-201,共5页Industrial Health and Occupational Diseases

基　　金：国家自然科学基金项目(30271113);国家973项目(2002CB512902)。

摘　　要：目的 探讨细胞色素CYP1A1酶的基因多态与慢性苯中毒遗传易感性的关系。方法采用病例对照设计,以268名苯中毒工人为病例组,268名接触苯而无中毒表现的工人为对照组。应用TaqManPCR分析技术检测CYP1A1基因rs1048943,rs4646421,rs4646422和rs4646903共4个SNPs位点。结果 CYP1A1基因rs1048943,rs4646421,rs4646422和rs46469034的不同基因型在病例组和对照组间的分布差异无统计学意义（P〉0.05）;单倍型分析显示,病例组中携带CYP1A1基因Hap5（rs4646421-T、rs4646422-G、rs1048943-A和rs4646903-C）单倍型个体的比例显著低于对照组（14.18%vs.19.40%）,携带此单倍型的个体慢性苯中毒的发病风险是携带Hap1（rs4646421-C、rs4646422-G、rs1048943-A和rs4646903-T）单倍型个体的0.708倍（OR=0.708,95%CI：0.503-0.998,P=0.048）。多因素Logistic回归分析提示,吸烟对慢性苯中毒发病风险具有一定的修饰作用（OR=0.19,95%CI：0.07-0.57,P=0.003）。结论 该研究人群携带CYP1A1基因Hap5单倍型个体可降低慢性苯中毒的发病风险,但CYP1A1基因多态与慢性苯中毒的遗传易感性的相关关系仍需进一步研究。Objective To explore the association between genetic polymorphisms in CYP1A1 and susceptibility to chronic benzene poisoning （CBP）. Methods A case-control study was conducted. 268 CBP patients and 268 workers occupationally exposed to benzene without poisoning manifestations were investigated. 4 SNPs （rs1048943, rs4646421, rs4646422 and rs4646903） of CYPIA1 gene were tested by the TaqMan PCR method. Results There was no significant difference for the distribution of genotypes of CYP1A1 rs1048943, rs4646421, rs4646422 and rs4646903 in the case and the control groups. Haplotypes analysis of polymorphisms in CYPIA1 showed that the proportion of the subjects carrying alleles of CYPIA1 rs4646421-T, rs4646422-G, rs1048943-A and rs4646903-C at the same time （Hap5） in the case group was lower than that of the control group （14.18% vs. 19.40%）, and compared with those carrying alleles of CYP1A1 rs4646421-C, rs4646422-G, rs1048943-A and rs4646903-T simultaneously （Hap1）, there was a 0.708-fold （0R=0.708, 95%CI： 0. 503-0. 998, P=0.048） decreased risk of CBP. Logistic regression analysis showed that smoking may play some role in modifying the risk of CBP （OR=O. 19, 95%CI： 0.07-0.57, P=0.003）. Conclusions In this population those subjects carrying haplotype 5 of CYP1A1 could decrease the risk of CBP. However, further studies are needed on the association between the genetic polymorphisms in CYP1A1 and the risk of CBP.

关 键 词：苯中毒 细胞色素P450 1A1 单核苷酸多态(SNP) 

分 类 号：R135.12[医药卫生—劳动卫生]