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European Journal of Clinical Pharmacology
Article . 2006 . Peer-reviewed
License: Springer TDM
Data sources: Crossref
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CYP2E1 genotype and isoniazid-induced hepatotoxicity in patients treated for latent tuberculosis

Authors: Vuilleumier, Nicolas; Rossier, Michel; Chiappe, Alberto; Degoumois, Florence; Dayer, Pierre; Mermillod, Bernadette; Nicod, Laurent; +2 Authors

CYP2E1 genotype and isoniazid-induced hepatotoxicity in patients treated for latent tuberculosis

Abstract

To determine whether pharmacogenetic tests such as N-acetyltransferase 2 (NAT2) and cytochrome P450 2E1 (CYP2E1) genotyping are useful in identifying patients prone to antituberculosis drug-induced hepatotoxicity in a cosmopolite population.In a prospective study we genotyped 89 patients treated with isoniazid (INH) for latent tuberculosis. INH-induced hepatitis (INH-H) or elevated liver enzymes including hepatitis (INH-ELE) was diagnosed based on the clinical diagnostic scale (CDS) designed for routine clinical practice. NAT2 genotypes were assessed by fluorescence resonance energy transfer probe after PCR analysis, and CYP2E1 genotypes were determined by PCR with restriction fragment length polymorphism analysis.Twenty-six patients (29%) had INH-ELE, while eight (9%) presented with INH-H leading to INH treatment interruption. We report no significant influence of NAT2 polymorphism, but we did find a significant association between the CYP2E1 *1A/*1A genotype and INH-ELE (OR: 3.4; 95% CI:1.1-12; p = 0.02) and a non significant trend for INH-H (OR: 5.9; 95% CI: 0.69-270; p = 0.13) compared with other CYP2E1 genotypes. This test for predicting INH-ELE had a positive predictive value (PPV) of 39% (95% CI: 26-54%) and a negative predictive value (NPV) of 84% (95% CI: 69-94%).The genotyping of CYP2E1 polymorphisms may be a useful predictive tool in the common setting of a highly heterogeneous population for predicting isoniazid-induced hepatic toxicity. Larger prospective randomized trials are needed to confirm these results.

Country
Switzerland
Keywords

Adult, Male, Positive predictive value, Adolescent, Genotype, Arylamine N-Acetyltransferase, Antitubercular Agents, Negative predictive value, 576, Gene Frequency, 615, Isoniazid, Humans, CYP2E1 TaqI polymorphism, Prospective Studies, Aged, DNA Primers, Base Sequence, Isoniazid-induced hepatitis, Cytochrome P-450 CYP2E1, Middle Aged, Cosmopolite population, NAT2 genotype, Liver, Pharmacogenetics, Female, Chemical and Drug Induced Liver Injury, Polymorphism, Restriction Fragment Length, ddc: ddc:576, ddc: ddc:615

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    popularity
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    Top 10%
    influence
    This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
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    impulse
    This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
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selected citations
These citations are derived from selected sources.
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
148
Top 10%
Top 10%
Top 10%
Green
bronze