Association between CYP2E1 and GOT2 gene polymorphisms and susceptibility and low-dose N,N-dimethylformamide occupational exposure-induced liver injury

Int Arch Occup Environ Health. 2019 Oct;92(7):967-975. doi: 10.1007/s00420-019-01436-1. Epub 2019 Apr 16.

Abstract

Objective: To investigate the effects of the interactions between the CYP2E1 and GOT2 gene polymorphisms and N,N-dimethylformamide (DMF) on liver injury.

Methods: A total of 672 DMF-exposed workers were randomly selected from two synthetic leather enterprises in Suzhou, China, for follow-up in a cohort study. Information on exposure to DMF in the air was collected through a fixed-point air sampler in the worker's breathing zone. The subjects were assessed every year during the period of 2010-2015, they underwent occupational health examinations. Alanine aminotransferase and aspartate aminotransferase levels were measured. Peripheral blood was collected and DNA was extracted. The genotypes rs2031920, rs3813867 and rs6413432 of the CYP2E1 gene and rs7204324 of the GOT2 gene were detected by PCR, and analyzed using the Chi-square test and logistic regression analysis.

Results: Workers exposed to a high cumulative dose of DMF were significantly more likely than low-exposed workers to develop liver injury. No association was observed between rs2031920, rs3813867 and rs6413432 of the CYP2E1 gene and DMF-induced liver damage. However, the A allele of rs7204324 on the GOT2 gene may be a risk factor for susceptibility to DMF-induced liver injury.

Conclusion: Polymorphisms of rs7204324 on GOT2 may play an important role in susceptibility to liver injury following exposure to DMF.

Keywords: CYP2E1; GOT2; Liver injury; N,N-Dimethylformamide; Occupational exposure.

MeSH terms

  • Adult
  • Air Pollutants, Occupational / adverse effects
  • Aspartate Aminotransferases / genetics*
  • Chemical and Drug Induced Liver Injury, Chronic / epidemiology
  • Chemical and Drug Induced Liver Injury, Chronic / genetics*
  • China
  • Cohort Studies
  • Cytochrome P-450 CYP2E1 / genetics*
  • Dimethylformamide / poisoning*
  • Environmental Monitoring
  • Female
  • Humans
  • Male
  • Middle Aged
  • Occupational Exposure / adverse effects*
  • Polymorphism, Genetic
  • Risk Factors

Substances

  • Air Pollutants, Occupational
  • Dimethylformamide
  • Cytochrome P-450 CYP2E1
  • Aspartate Aminotransferases