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


CONCLUSIONS
Gene-gene, gene-environment interactions are important mechanism to genetic susceptibility of CBP.
Department of Occupational Health, School of Public Health, Fudan University, Shanghai 200032, China.
Ru-Feng
RF
Jin
Jun-Xiang
JX
Wan
Shou-Yong
SY
Gu
Pin
P
Sun
Zhong-Bin
ZB
Zhang
Xi-Peng
XP
Jin
Zhao-Lin
ZL
Xia
D000328:Adult; D001554:Benzene / Q000506:poisoning*; D016022:Case-Control Studies; D019363:Cytochrome P-450 CYP1A1 / Q000235:genetics; D019389:Cytochrome P-450 CYP2D6 / Q000235:genetics; D019392:Cytochrome P-450 CYP2E1 / Q000235:genetics*; D004851:Epoxide Hydrolases / Q000235:genetics; D005260:Female; D059647:Gene-Environment Interaction; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D058011:Multifactor Dimensionality Reduction; D016273:Occupational Exposure; D020641:Polymorphism, Single Nucleotide; D055815:Young Adult
D019392:Cytochrome P-450 CYP2E1; D019363:Cytochrome P-450 CYP1A1; D019389:Cytochrome P-450 CYP2D6; D004851:Epoxide Hydrolases; D001554:Benzene