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

Our plain-English summary of Decreased Cyp2E1 mRNA expression in human leucocytes in patients with fibrotic and inflammatory lung diseases, by S. Helmig, J. Döhrel, J. Schneider (International Journal of Molecular Medicine, 2010).

The study

• Authors: S. Helmig, J. Döhrel, J. Schneider
• Journal: International Journal of Molecular Medicine
• Published: 2010;26(1):143-9
• Cited by: 6 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

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(-DeltaDeltaCT) 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.

In plain English

This German laboratory study measured messenger RNA (mRNA) for CYP2E1, an enzyme involved in processing many chemicals, in white blood cells. The authors compared 137 patients with fibrotic and inflammatory lung diseases with 221 healthy controls, all Caucasian, from Giessen. Compared with healthy controls (mean 0.026, n=206), expression was significantly lower in patients with fibrotic lung diseases, a group including asbestosis and silicosis (0.016, n=52), and in patients with other inflammatory lung diseases (0.013, n=16). The lower level in obstructive airway diseases (0.020, n=64) was not statistically significant. Asbestos-exposed people had significantly lower expression (0.019, n=40) than unexposed controls (0.026, n=197); the silica-exposed group did not reach significance. Patients with recognised occupational lung or pleural asbestosis also had significantly lower expression (0.018, n=31). No relevant differences appeared by smoking status or sex, and links with body mass index and age were very weak; the authors concluded these factors did not influence expression. The authors concluded that expression was decreased in fibrotic and inflammatory lung disease. They noted it is unknown whether blood-cell results reflect lung processes, and that mRNA need not reflect enzyme activity.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Laboratory comparison of gene expression and genotype in blood cells of lung disease patients versus healthy controls
• Who was studied: 358 Caucasians in Giessen, Germany: 221 healthy controls (mean age 27; hospital staff and students) and 137 patients with fibrotic and inflammatory lung diseases (mean age 62), including patients recruited at the Policlinic of the Institute for Occupational and Social Medicine
• Exposure: Occupational exposure to asbestos (fiber type not specified), silica, organic dust and irritative chemicals, plus smoking; also recognised occupational diseases including No. 4103, lung or pleural asbestosis
• Main results:
  • Mean relative CYP2E1 mRNA expression (plus or minus standard error) was significantly lower in fibrotic lung disease patients (0.016 plus or minus 0.002, n=52) and inflammatory lung disease patients (0.013 plus or minus 0.002, n=16) than in healthy controls (0.026 plus or minus 0.002, n=206)
  • In obstructive airway disease patients, expression was also lower (0.020 plus or minus 0.002, n=64, p=0.053), but this was not statistically significant
  • The asbestos-exposed group had significantly reduced expression (0.019 plus or minus 0.003, n=40, p=0.016). The silica-exposed group did not (0.016 plus or minus 0.005, n=13, p=0.095). Both were compared with unexposed healthy controls (0.026 plus or minus 0.002, n=197)
  • Groups exposed to organic dust (0.016 plus or minus 0.003, n=39) and irritative chemicals (0.016 plus or minus 0.002, n=22) had significantly reduced expression
  • Patients with recognised occupational lung or pleural asbestosis (No. 4103) had significantly reduced expression (0.018 plus or minus 0.003, n=31, p=0.024). Patients with silicosis (No. 4101) did not (0.018 plus or minus 0.008, n=8, p=0.410). Both were compared with healthy controls (0.026 plus or minus 0.002, n=206)
  • Patients with recognised allergic obstructive airway diseases (No. 4301; 0.013, n=23), exogenic allergic alveolitis (No. 4201; 0.009, n=6) and obstructive airway diseases caused by irritative chemicals (No. 4302; 0.013, n=11) had significantly reduced expression
  • Carriers of the rare c2 allele tended to have higher expression, but the difference from the c1/c1 genotype was not statistically significant
  • No relevant differences in expression were found between smokers, non-smokers and ex-smokers or between males and females (data not shown)
  • Relationships of expression with body mass index (R-squared 0.032 overall) and age (R-squared 0.011 overall) were very weak. From these analyses, the authors concluded that smoking, gender, body mass index and age did not influence expression
• The authors' conclusion: The authors concluded that CYP2E1 mRNA expression was significantly decreased in patients with fibrotic and inflammatory lung diseases compared with healthy controls
• Limitations the authors state:
  • Only 22 carriers of the rare c2 allele were found, so the genotype comparison did not reach significance
  • mRNA levels do not necessarily reflect enzyme activity
  • Inflammatory cytokine levels were not measured, and the effect of decreased mRNA on the protein was not determined
  • It is not known whether results from white blood cells reflect processes in organs such as the lung

Topics

Medical terms in this study, explained in our Lexicon: Occupational Disease.

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