Association between polymorphism of GSTP1, GSTT1, GSTM1 and CYP2E1 genes and susceptibility to benzene-induced hematotoxicity

Arch Toxicol. 2018 Jun;92(6):1983-1990. doi: 10.1007/s00204-017-2104-9. Epub 2017 Dec 4.


Occupational exposure to benzene has been associated with leukemia, anemia, leukopenia, and thrombocytopenia. Genetic susceptibility to benzene toxicity in humans may be related to variations in benzene metabolizing genes. The main objective of this study was to ascertain whether polymorphism of GSTP1, GSTM1, GSTT1 and CYP2E1 genes might influence susceptibility to the adverse effects of benzene among employees of a petrochemical plant. In this cross-sectional study, 124 employees of a petrochemical plant who had been occupationally exposed to benzene and had one or more abnormal hematological parameter (cases) and 184 subjects with a similar exposure scenario, free from any abnormal hematological parameters (referent) were studied. Atmospheric concentrations of benzene were measured and GSTM1 and GSTT1 genotypes were evaluated using the multiplex polymerase chain reaction (PCR) technique. Additionally, GSTP1 and CYP2E1 genotypes were determined by PCR- restriction fragment length polymorphism (PCR-RFLP). The frequency of null GSTT1 genotype in cases was significantly higher than that of referent group (32.3 vs. 18.5%, OR 2.1, 95% CI 1.23-3.56, p = 0.004). The mean value of platelets in subjects with null GSTT1 genotype was significantly lower than that of individuals with positive GSTT1 genotype (p = 0.015). Conversely, the mean value of leukocytes was significantly higher in subjects with null GSTM1 genotype as compared to those with positive GSTM1 genotype (p = 0.026). Logistic regression analysis showed that, subjects with null GSTT1 genotype had a significantly higher risk for hematological disorders, as compared to those with positive GSTT1 genotype (OR 2.1, 95% CI 1.23-3.56). Moreover, subjects with both null GSTT1 and GSTM1 genotypes had a significantly higher risk for hematological disorders as compared to subjects with positive GSTT1 and GSTM1 genotypes (OR 2.35, 95% CI 1.14-4.8). The results of this study showed that, individuals carrying null GSTT1 or both null STT1 and GSTM1 genotypes had a higher risk and were more susceptible to benzene-induced hematological disorders.

Keywords: Genetic polymorphism; Petrochemical employees; Susceptibility to benzene-induced hematotoxicity.

MeSH terms

  • Adult
  • Air Pollutants, Occupational / metabolism
  • Air Pollutants, Occupational / toxicity*
  • Benzene / metabolism
  • Benzene / toxicity*
  • Cross-Sectional Studies
  • Cytochrome P450 Family 2 / genetics
  • Erythrocytes / drug effects
  • Genetic Predisposition to Disease*
  • Glutathione S-Transferase pi / genetics
  • Glutathione Transferase / genetics
  • Hematologic Diseases / blood
  • Hematologic Diseases / chemically induced*
  • Hemoglobins / analysis
  • Humans
  • Iran
  • Leukocytes / drug effects
  • Logistic Models
  • Occupational Exposure / adverse effects*
  • Occupational Exposure / analysis
  • Polymorphism, Restriction Fragment Length*
  • Risk


  • Air Pollutants, Occupational
  • Hemoglobins
  • CYP2F1 protein, human
  • Cytochrome P450 Family 2
  • glutathione S-transferase T1
  • GSTP1 protein, human
  • Glutathione S-Transferase pi
  • Glutathione Transferase
  • glutathione S-transferase M1
  • Benzene