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Decreased Cyp2E1 mRNA expression in human leucocytes in patients with fibrotic and inflammatory lung diseases

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Cytochrome P450 2E1 (CYP2E1), a phase I enzyme, is involved in the activation of a broad spectrum of pro-carcinogens. The importance of this enzyme for pharmacology is derived from its unique substrate spectrum. Large inter-individual differences in the toxicity of its substrates are known. We investigated the quantitative Cyp2E1 mRNA expression in a cohort of patients with fibrotic and inflammatory lung diseases (n=137) and healthy controls (n=221) considering tobacco-smoke, exposure to asbestos, silica, organic dust or chemical irritating particles in relation to the C1053T (RsaI) polymorphism of Cyp2E1. For quantitative comparison of Cyp2E1 mRNA levels real-time PCR was performed using a LightCycler® System. Calculations of expression were made with the 2-ΔΔCT method. Detection of the C1053T (RsaI) polymorphism of the Cyp2E1 gene was performed by rapid capillary PCR with melting curve analysis. Fibrotic (0.016±0.002; n=52; p=0.000) and inflammatory (0.013±0.002; n=16, p=0.000) lung disease patients showed a significantly reduced Cyp2E1 mRNA expression compared to healthy controls (0.026±0.002; n=206). Exposure to asbestos (0.019±0.003; n=40; p=0.016), organic dust (0.016±0.003; n=39; p=0.000) and irritative chemicals (0.016±0.002; n=22; p=0.000) revealed a highly significant reduced Cyp2E1 expression. Cyp2E1 mRNA expression of occupational disease (OD) patients suffering from lung or pleural asbestosis OD-No. 4103 (0.018±0,003; n=31; p=0.024), allergic obstructive airway diseases OD-No. 4301 (0.013±0.002; n=23; p=0.000), exogenic allergic alveolitis OD-No. 4201 (0.009±0.002; n=6; p=0.000) and obstructive airway diseases caused by irritative chemicals OD-No. 4302 (0.013±0.001; n=11; p=0.000) was highly significantly reduced. In conclusion, we demonstrated a significantly decreased mRNA expression in patients with fibrotic and inflammatory lung diseases compared to healthy controls.
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Document Type: Research Article

Affiliations: Institut und Poliklinik für Arbeits- und Sozialmedizin, der Justus-Liebig Universität, D-35392 Giessen, Germany., Email: [email protected]

Publication date: July 1, 2010

More about this publication?
  • The International Journal of Molecular Medicine is a monthly, peer-reviewed journal devoted to the publication of high quality studies related to the molecular mechanisms of human disease. The journal welcomes research on all aspects of molecular and clinical research, ranging from biochemistry to immunology, pathology, genetics, human genomics, microbiology, molecular pathogenesis, molecular cardiology, molecular surgery and molecular psychology.

    The International Journal of Molecular Medicine aims to provide an insight for researchers within the community in regard to developing molecular tools and identifying molecular targets for the diagnosis and treatment of a diverse number of human diseases.
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