Human cytochrome from genotype to phenotype

Carrière, Véronique; Berthou, F.; Baird, Scott Everet; Belloc, C.; Beaune, Philippe; Waziers, de

doi:10.1097/00008571-199606000-00002

Cited by 118 publications

(62 citation statements)

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“…Still our result is affirmed by gene analyses, which indicate that the rare c2 allele is accompanied with a higher mRNA expression (12,13). Increased mRNA expression does not necessarily reflect enzyme activity level, but still evidence was obtained on increased catalytic activity of the enzyme coded by the c2 allele (13,20). Cyp2E1 is involved in the metabolism of many procarcinogens and possesses the ability to reduce molecular oxygen to highly reactive compounds, leading to intensified lipid and protein peroxidation, DNA damage and carcinogenesis (21).…”

Section: Discussionsupporting

confidence: 59%

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

Helmig

Döhrel²,

Schneider³

2010

Int J Mol Med

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Abstract. Cytochrome P450 2E1 (CYP2E1), a phase I enzyme, is involved in the activation of a broad spectrum of procarcinogens. The importance of this enzyme for pharmacology is derived from its unique substrate spectrum. Large interindividual 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 ODNo. 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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Section: Discussionsupporting

confidence: 59%

“…Striking inter-ethnic differences, complicating analysis, appear with respect to the rare c2 alleles frequency. The rare allele frequencies reported are 24-30% for Asians (15,27,28), 2-3% for Caucasians (20,27), 0.3-7% for Afro-Americans (27,29,30), 15% for Mexican-Americans (29) and 18% for Taiwanese (31).…”

Section: Discussionmentioning

confidence: 95%

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

Helmig

Döhrel²,

Schneider³

2010

Int J Mol Med

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“…Watanabe et al 39 and Hayashi et al 15 reported that the RsaI variant c2 allele produced higher enzyme activity than the c1/c1 genotype in Japanese individuals, although this finding is itself controversial. [40][41][42] Highly activated CYP2E1 induced by alcohol may play a more important role in the metabolic activation of several tobacco-specific procarcinogens, including various nitrosamines. It has been suggested that these low-molecular-weight carcinogens are associated with the development of peripheral adenocarcinoma.…”

Section: Discussionmentioning

confidence: 99%

Susceptibility to lung cancer and genetic polymorphisms in the alcohol metabolite‐related enzymes alcohol dehydrogenase 3, aldehyde dehydrogenase 2, and cytochrome P450 2E1 in the Japanese population

Minegishi

Tsukino²,

Muto

et al. 2007

Cancer

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BACKGROUND.It is believed that acetaldehyde plays an important role in alcohol‐related carcinogenesis; although current epidemiologic studies have provided inconsistent findings on the association between alcohol consumption and the risk of lung cancer.METHODS.To clarify the hypothesis that genetic polymorphisms in alcohol‐metabolizing enzymes may influence susceptibility to lung cancer, the authors conducted a hospital‐based case‐control study and examined genetic polymorphisms in the alcohol dehydrogenase 3, aldehyde dehydrogenase 2 (ALDH2), and cytochrome P450 2E1 genes in 505 patients with histologically confirmed lung cancer and in a group of 256 noncancer controls who provided complete cigarette and alcohol consumption histories. Genotyping was conducted by polymerase chain reaction‐restriction fragment‐length polymorphism assay.RESULTS.A significant association was noted between alcohol consumption and lung cancer risk. Thus, using the median value for the controls as the cut‐off point, the odds ratios (OR) for light and heavy drinkers were 1.76 and 1.95, respectively (P for trend = .012), compared with nondrinkers. In addition, there was a significant trend toward increased risk of lung cancer in drinkers with ALDH2 variant alleles (P for trend <.0001). The adjusted OR for heavy drinkers was 6.15 compared with nondrinkers. Regarding associations between histologic type and genotypes, the ALDH2 variant allele was significantly less common in patients who had adenocarcinoma compared with controls.CONCLUSIONS.The current observations suggested a positive association between alcohol consumption and the risk of lung cancer: Drinking may increase the risk, especially among individuals who have the variant ALDH2 alleles. Cancer 2007. © 2007 American Cancer Society.

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“…Some of the previous studies have shown findings on CYP2E1 polymorphism associations with CYP2E1 activities and HCC risk (Hayashi et al, 1991;Ladero et al, 1996;Lucas et al, 1995;Marchand et al, 1999;Watanabe et al, 1994;Yu et al, 1995). However, other previous studies have reported that there was no association between CYP2E1 genetic polymorphisms and CYP2E1 activities (Carriere et al, 1996;Inoue et al, 2000;Powell et al, 1998). In other words, including the findings of this study, the literature have shown contradictory findings on associations of CYP2E1 polymorphisms with CYP2E1 activities and HCC risk, especially rs3813867 polymorphism which is in absolute linkage disequilibrium (LD) (|D'|=1 and r 2 =1) with RsaI polymorphism (CYP2E1*5B) (rs2031920), which is associated with higher transcription, increased enzyme activity, and alcoholic liver disease (Grove et al, 1998;Hayashi et al, 1991;Piao et al, 2003;Tanaka et al, 1997;Tsutsumi et al, 1994).…”

Section: Discussionmentioning

confidence: 94%

Identification of Polymorphisms in CYP2E1 Gene and Association Analysis among Chronic HBV Patients

Chun¹,

Park²,

Cheong³

et al. 2009

Genomics & Informatics

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Cytochrome P450 2E1 (CYP2E1) is a member of the cytochrome P450 superfamily, and it is a key enzyme responsible for the metabolic activation of many smallmolecular-weight compounds such as alcohol, which is classified as a human carcinogen. In this study, we identified 19 single nucleotide polymorphisms (SNPs) in CYP2E1 in Korean population. In these SNPs, we examined possible genetic association of CYP2E1 polymorphisms with HBV clearance and the risk of hepatocellular carcinoma (HCC). Five common polymorphic sites were selected, CYP2E1 polymorphisms at rs381-3867, rs3813870, rs2070673, rs2515641 and rs2480257, considering their allele frequencies, haplotype-tagging status and LDs for genotyping in larger-scale subjects (n=1,092). Statistical analysis demonstrated that CYP2E1 polymorphisms and haplotypes show no significant association with HBV clearance, HCC occurrence and onset age of HCC (p＞0.05). Previous studies, however, have shown contradictory findings on associations of CYP2E1 polymorphisms with CYP2E1 activities and HCC risk. Comparing the contrasting results of previous researches suggest that CYP2E1 polymorphism is associated with CYP2E1 activity induced by ethanol, but is not directly associated with HCC risk. CYP2E1 variation/haploype information identified in this study will provide valuable information for future studies on CYP2E1.

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Human cytochrome from genotype to phenotype

Cited by 118 publications

References 0 publications

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

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

Susceptibility to lung cancer and genetic polymorphisms in the alcohol metabolite‐related enzymes alcohol dehydrogenase 3, aldehyde dehydrogenase 2, and cytochrome P450 2E1 in the Japanese population

Identification of Polymorphisms in CYP2E1 Gene and Association Analysis among Chronic HBV Patients

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