Titre
CYP2E1 genotype and isoniazid-induced hepatotoxicity in patients treated for latent tuberculosis.
Type
article
Institution
Externe
Périodique
Auteur(s)
Vuilleumier, N.
Auteure/Auteur
Rossier, M.F.
Auteure/Auteur
Chiappe, A.
Auteure/Auteur
Degoumois, F.
Auteure/Auteur
Dayer, P.
Auteure/Auteur
Mermillod, B.
Auteure/Auteur
Nicod, L.
Auteure/Auteur
Desmeules, J.
Auteure/Auteur
Hochstrasser, D.
Auteure/Auteur
Liens vers les personnes
ISSN
0031-6970[print], 0031-6970[linking]
Statut éditorial
Publié
Date de publication
2006
Volume
62
Numéro
6
Première page
423
Dernière page/numéro d’article
429
Langue
anglais
Résumé
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.
Sujets
PID Serval
serval:BIB_9C280500C91E
PMID
Date de création
2010-02-19T18:18:08.590Z
Date de création dans IRIS
2025-05-20T22:38:59Z