Decreased Cyp2E1 mRNA expression in human leucocytes in patients with fibrotic and inflammatory lung diseases.
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.
Institut und Poliklinik für Arbeits- und Sozialmedizin, der Justus-Liebig Universität, D-35392 Giessen, Germany. simone.helmig@arbmed.med.uni-giessen.de
Simone
S
Helmig
Juliane
J
Döhrel
Joachim
J
Schneider
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000704:Analysis of Variance; D019392:Cytochrome P-450 CYP2E1 / Q000235:genetics*; D005260:Female; D020869:Gene Expression Profiling; D015971:Gene Expression Regulation, Enzymologic; D005787:Gene Frequency; D006801:Humans; D007962:Leukocytes / Q000201:enzymology / Q000378:metabolism*; D015810:Linkage Disequilibrium; D008171:Lung Diseases / Q000201:enzymology / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009784:Occupational Diseases / Q000201:enzymology / Q000235:genetics; D011014:Pneumonia / Q000201:enzymology / Q000235:genetics; D011110:Polymorphism, Genetic; D011658:Pulmonary Fibrosis / Q000201:enzymology / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D055815:Young Adult
D012333:RNA, Messenger; D019392:Cytochrome P-450 CYP2E1