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

Zhonghua Lao Dong Wei Sheng Zhi Ye Bing Za Zhi. 2011 Jul;29(7):481-6.
[Article in Chinese]


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. 30 single 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 GSTP1 rs947894, 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 3 types of interactions were as followed: interactions of GSTP1 rs947894 with alcohol consumption, CYP2E1 rs3813867 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 CYP2D6 rs1135840.

Conclusion: Gene-gene, gene-environment interactions are important mechanism to genetic susceptibility of CBP.

Publication types

  • English Abstract
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adult
  • Benzene / poisoning*
  • Case-Control Studies
  • Cytochrome P-450 CYP1A1 / genetics
  • Cytochrome P-450 CYP2D6 / genetics
  • Cytochrome P-450 CYP2E1 / genetics*
  • Epoxide Hydrolases / genetics
  • Female
  • Gene-Environment Interaction
  • Genetic Predisposition to Disease
  • Genotype
  • Humans
  • Logistic Models
  • Male
  • Middle Aged
  • Multifactor Dimensionality Reduction
  • Occupational Exposure*
  • Polymorphism, Single Nucleotide
  • Young Adult


  • Cytochrome P-450 CYP2E1
  • Cytochrome P-450 CYP1A1
  • Cytochrome P-450 CYP2D6
  • Epoxide Hydrolases
  • Benzene