代谢酶基因多态性与慢性苯中毒关联的logistic回归与多因子降维法分析  

Association analysis of polymorphisms of metabolizing enzyme genes with chronic benzene poisoning based on logistic regression and multifactor dimensionality reduction

作　　者：金如锋[1] 万俊香[1] 顾寿永[1] 孙品[1] 张忠彬[1] 金锡鹏[1] 夏昭林[1] 

机构地区：[1]复旦大学公共卫生学院劳动卫生教研室,上海200032

出　　处：《中华劳动卫生职业病杂志》2011年第7期481-486,共6页Chinese Journal of Industrial Hygiene and Occupational Diseases

基　　金：国家自然科学基金资助项目（30271113）;科技部＂973＂项目（2002CB512902）;上海市劳动卫生学重点学科建设计划（08GWZX0402）

摘　　要：目的 研究多种代谢酶基因多态性与慢性苯中毒的关联.方法 采用病例-对照研究,以152名苯中毒工人为病例组,152名接触苯而没有中毒表现的工人为对照组.应用聚合酶链反应-限制性片段长度多态性（PCR-RFLP）、测序等技术检测CYP2E1等13个基因的30个单核苷酸多态性（SNP）.Logistic回归模型分析主效应和2阶交互作用,多因子降维法分析高阶交互作用.结果 logistic回归分析表明,控制了性别、吸烟、饮酒、苯接触强度的影响后,GSTP1 rs947894、CYP1A1rs4646903、CYP2D6 rs1065852、CYP2D6 rs1135840有主效应（P＜0.05）.EPHX1 rs1051740可能有主效应（P=0.06）.GSTP1 rs947894与饮酒有交互作用;CYP2E1 rs3813867和EPHX1 rs3738047无主效应,但有交互作用;EPHX1 rs3738047与饮酒也有交互作用.未发现其他SNP与慢性苯中毒的关联.多因子降维法模型发现了1个联合作用最强的3阶交互作用,即CYP1A1 rs4646903、CYP2D6 rs1065852、CYP2D6rs1135840的3因子组合.结论 基因-基因、基因-环境交互作用是影响个体慢性苯中毒遗传易感性的重要方式.Objective To explore the association of polymorphisms of metabolizing enzyme genes with chronic benzene poisoning（CBP） comprehensively by case-control design. Methods 152 CBP patients and 152 workers occupationally exposed to benzene without poisoning manifestations were investigated. 30single nucleotide polymorphisms （SNPs） in 13 genes such as CYP2E1 were tested by PCR-RFLP, sequencing approaches. Logistic regression model was used to detect main effects and 2-order interaction effects of gene and/or environment. Multifactor dimensionality reduction （MDR） was used to detect high-order gene-gene or gene-environment interactions. Results Based on logistic regression, the main effects of G57P7rs947894,EPHX1 rs1051740, CYP1A1 rs4646903, CYP2D6 rs1065852 and rs1135840 were found to be significant （P〈0.05） while the confounding factors of sex, cigarette smoking, alcohol consumption and the intensity of benzene exposure were controlled. EPHX1 rs1051740 might be associated with CBP （P=0.06）. There existed 3types of interactions were as followed： interactions of GSTP1 rs947894 with alcohol consumption, CYP2E1rs3813867 with EPHX1 rs3738047, EPHX1 rs3738047 with alcohol consumption（P〈0.05）, while the main effects of CYP2E1 rs3813867 and EPHX1 rs3738047 were not significant （P〉0.05）. The other SNPs did not show any significant associations with CBP. According to MDR, a 3-order interaction with the strongest combined effect was found, i.e. the 3-factor combination of CYP1A1 rs4646903, CYP2D6 rs1065852 and CYP2D6rs1135840. Conclusion Gene-gene, gene-environment interactions are important mechanism to genetic susceptibility of CBP.

关 键 词：苯 中毒 多态性 单核苷酸 模型 统计学 

分 类 号：R686[医药卫生—骨科学]