Cytochrome P450 2E1 genotype and chlorzoxazone metabolism in healthy and alcoholic Caucasian subjects

Lucas, Danièle; Ménez, Catherine; Girre, Catherine; Berthou, F.; Bodénez, Pierre; Joannet, I.; Hispard, Eric; Bardou, Louis-georges; Ménez, J. F.

doi:10.1097/00008571-199510000-00005

Cited by 129 publications

(83 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…However, the distribution of CYP2E1 and ADH 3 genotypes was not significantly different among the disease groups, though the power to detect such differences is low. In addition, frequencies of CYP2E1 C or c2 alleles in our control population (6.4% and 2.3%, respectively) were in agreement with those previously reported in Caucasians (Kato et al, 1992;Lucas et al, 1995;Matthias et al, 1998;Stephens et al, 1994). The ADH 3 allele frequencies among our control subjects (0.57 for ADH 3 1 and 0.43 for ADH 3 2) were also similar to those reported for French subjects (0.55 and 0.45, respectively) .…”

Section: Discussionsupporting

confidence: 93%

“…In our study population, the frequency of the C variant allele was about 3 times that of the rare c2 allele and no control individuals were homozygous for the c2 allele. We also confirmed that carriers of the c2 allele-specific mutation carried the C allele-specific one (Lucas et al, 1995;Persson et al, 1993), indicating a partial linkage of both alleles. It was therefore impossible to evaluate the effect of the DraI C allele among carriers of the RsaI c1c1 genotype and among those with c1c2 or c2c2 genotypes.…”

Section: Discussionsupporting

confidence: 75%

“…However, to date, there is only little evidence that the variant alleles are related to enhanced CYP2E1 activity in vivo. Studies among Caucasians have demonstrated that heterozygous c1c2 or CD subjects displayed low-level CYP2E1 activity after chronic ethanol consumption, suggesting a lack of inducibility of the mutated genes (Lucas et al, 1995). This is in contrast with other studies performed in Asian subjects, among whom the frequency of the mutated alleles is higher, where CYP2E1 mRNA levels tended to be higher in the presence of C or c2 alleles (Tsutsumi et al, 1994;Uematsu et al, 1994).…”

Section: Discussionmentioning

confidence: 87%

See 2 more Smart Citations

Role of alcohol dehydrogenase 3 and cytochrome P‐4502E1 genotypes in susceptibility to cancers of the upper aerodigestive tract

et al. 2000

View full text Add to dashboard Cite

Alcohol is a recognized risk factor for upper aerodigestive tract (UAT) cancers, but the mechanism by which alcohol causes cancer remains obscure. Ethanol is oxidized to acetaldehyde (the suspected carcinogenic agent in alcohol) by alcohol dehydrogenases (ADHs) and cytochrome P-4502E1 (CYP2E1), both of which exhibit great inter-individual variability in activity. The hypothesis that these polymorphisms influence susceptibility to alcohol-related cancers remains poorly documented. We investigated whether ADH 3 and CYP2E1 DraI and RsaI genotypes modified the risk of UAT cancers among 121 oral cavity/pharyngeal cancer patients, 129 laryngeal cancer patients, and 172 controls, all French Caucasians. Cancer risks and gene-alcohol interactions were analyzed by unconditional logistic regression, accounting for potential confounders. ADH 3 genotype was not associated with UAT cancer. In contrast, a 2-fold risk of oral cavity/ pharyngeal (OR ‫؍‬ 2.0, 95% CI 1.0 -3.9) and laryngeal (OR ‫؍‬ 1.8, 95% CI 1.0 -3.5) cancers was observed for carriers of the CYP2E1 DraI C variant allele compared with other individuals. The risk associated with the CYP2E1 RsaI c2 variant allele also increased for oral cavity/pharyngeal cancer (OR ‫؍‬ 2.6, 95% CI 1.0 -6.6). The effects of ADH 3 or CYP2E1 genotype and alcohol or tobacco were independent. The highest risk of oral cavity/pharyngeal cancer was observed among the heaviest drinkers (>80 g/day) with the CYP2E1 DraI C allele (OR ‫؍‬ 5.8, 95% CI 1.9 -18.2) or the CYP2E1 RsaI c2 allele (OR ‫؍‬ 7.2, 95% CI 1.4 -38.2) compared with lighter drinkers with other genotypes. Our study suggests that CYP2E1 genotype modifies the risk of UAT cancers, but due to the low frequency of CYP2E1 variant alleles, large-scale studies are needed to confirm our findings. Int.

show abstract

Section: Discussionsupporting

confidence: 93%

Section: Discussionsupporting

confidence: 75%

Section: Discussionmentioning

confidence: 87%

See 1 more Smart Citation

Role of alcohol dehydrogenase 3 and cytochrome P‐4502E1 genotypes in susceptibility to cancers of the upper aerodigestive tract

et al. 2000

View full text Add to dashboard Cite

show abstract

“…30 The serum 6-OH-CZX/CZX concentration ratio has been shown to reflect the rate of CZX hydroxylation and thus represent the CYP2E1 activity. [30][31][32] To study the effect of isoniazid on the CYP2E1 activity in subjects with different CYP2E1 genotypes, isoniazid 300 mg daily was administered for 7 days (days 1 to 7). The CZX test was performed 1 day before the administration of isoniazid (day 0) and the last day of isoniazid intake (day 7).…”

Section: Methodsmentioning

confidence: 99%

Cytochrome P450 2E1 genotype and the susceptibility to antituberculosis drug-induced hepatitis

Yi¹,

et al. 2003

View full text Add to dashboard Cite

Most cases with antituberculosis drug-induced hepatitis have been attributed to isoniazid. Isoniazid is metabolized by hepatic N-acetyltransferase (NAT) and cytochrome P450 2E1 (CYP2E1) to form hepatotoxins. However, the role of CYP2E1 in this hepatotoxicity has not yet been reported. The aim of this study was to evaluate whether the polymorphism of the CYP2E1 gene is associated with antituberculosis drug-induced hepatitis. A total of 318 tuberculosis patients who received antituberculosis treatment were followed prospectively. Their CYP2E1 and NAT2 genotypes were determined using a polymerase chain reaction with restriction fragment length polymorphism method. Twenty-one healthy volunteers were recruited for CYP2E1 phenotype study using a chlorzoxazone test. Forty-nine (15.4%) patients were diagnosed to have drug-induced hepatotoxicity. Patients with homozygous wild genotype CYP2E1 c1/c1 had a higher risk of hepatotoxicity (20.0%; odds ratio [OR], 2.52) than those with mutant allele c2 (CYP2E1 c1/c2 or c2/c2, 9.0%, P ‫؍‬ .009). If CYP2E1 c1/c2 or c2/c2 genotype combined with rapid acetylator status was regarded as the reference group, the risk of hepatotoxicity increased from 3.94 for CYP2E1 c1/c1 with rapid acetylator status to 7.43 for CYP2E1 c1/c1 with slow acetylator status. After adjustment for acetylator status and age, the CYP2E1 c1/c1 genotype remained an independent risk factor for hepatotoxicity (OR, 2.38; P ‫؍‬ .017). Furthermore, under the administration of isoniazid, the volunteers with CYP2E1 c1/c1 genotype had higher CYP2E1 activity than those with other genotypes had and, hence, might produce more hepatotoxins. In conclusion, CYP 2E1 genetic polymorphism may be associated with susceptibility to antituberculosis drug-induced hepatitis. (HEPATOLOGY 2003;37:924-930.)

show abstract

“…Lucas et al' results showed that a substantially reduced chlorzoxazone 6-hydroxylation was observed in the single c2/c2 genotype carriers. Additionally, patients with the mutated genotype appeared to have less induction of CYP2E1 than wild-type carriers after ethanol administration (Lucas et al, 1995). Tan et al's results showed that the levels of CYP2E1 protein was significantly higher among subjects carrying the c1/ c1 genotype than that among those carrying c1/c2 or c2/ c2 genotype, and the mean activity of CYP2E1 towards Figure 3.…”

Section: Discussionmentioning

confidence: 95%

Updated Meta-analysis of the Association Between CYP2E1 RsaI/PstI Polymorphisms and Lung Cancer Risk in Chinese Population

Wang

Yang²,

Liu³

et al. 2014

Asian Pacific Journal of Cancer Prevention

View full text Add to dashboard Cite

Cytochrome P450 2E1 genotype and chlorzoxazone metabolism in healthy and alcoholic Caucasian subjects

Cited by 129 publications

References 0 publications

Role of alcohol dehydrogenase 3 and cytochrome P‐4502E1 genotypes in susceptibility to cancers of the upper aerodigestive tract

Role of alcohol dehydrogenase 3 and cytochrome P‐4502E1 genotypes in susceptibility to cancers of the upper aerodigestive tract

Cytochrome P450 2E1 genotype and the susceptibility to antituberculosis drug-induced hepatitis

Updated Meta-analysis of the Association Between CYP2E1 RsaI/PstI Polymorphisms and Lung Cancer Risk in Chinese Population

Contact Info

Product

Resources

About