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

Details

Serval ID
serval:BIB_9C280500C91E
Type
Article: article from journal or magazin.
Collection
Publications
Title
CYP2E1 genotype and isoniazid-induced hepatotoxicity in patients treated for latent tuberculosis.
Journal
European Journal of Clinical Pharmacology
Author(s)
Vuilleumier N., Rossier M.F., Chiappe A., Degoumois F., Dayer P., Mermillod B., Nicod L., Desmeules J., Hochstrasser D.
ISSN
0031-6970[print], 0031-6970[linking]
Publication state
Published
Issued date
2006
Volume
62
Number
6
Pages
423-429
Language
english
Abstract
OBJECTIVE: 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. METHODS: 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. RESULTS: 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%). CONCLUSION: 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.
Keywords
Adolescent, Adult, Aged, Antitubercular Agents/adverse effects, Antitubercular Agents/metabolism, Arylamine N-Acetyltransferase/genetics, Base Sequence, Cytochrome P-450 CYP2E1/genetics, DNA Primers/genetics, Drug-Induced Liver Injury/enzymology, Drug-Induced Liver Injury/etiology, Female, Gene Frequency, Genotype, Humans, Isoniazid/adverse effects, Isoniazid/metabolism, Liver/drug effects, Male, Middle Aged, Pharmacogenetics, Polymorphism, Restriction Fragment Length, Prospective Studies, Tuberculosis, Pulmonary/drug therapy
Pubmed
Create date
19/02/2010 19:18
Last modification date
20/08/2019 15:02
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