N-acetyltransferase 2 (NAT2) genotype as a risk factor for development of drug-induced liver injury relating to antituberculosis drug treatment in a mixed-ethnicity patient group.
Eur J Clin Pharmacol
; 70(9): 1079-86, 2014 Sep.
Article
en En
| MEDLINE
| ID: mdl-24888881
ABSTRACT
PURPOSE:
This study aims to assess whether NAT2 genotype affects susceptibility to moderate to severe liver injury in patients undergoing drug treatment for tuberculosis with isoniazid-containing regimens.METHODS:
Twenty-six patients of European or South Asian ethnicity, who had suffered liver injury during treatment with isoniazid-containing drug regimens and 101 ethnically matched controls were genotyped for the NAT2*5, NAT2*6, and NAT2*7 alleles. Genotyping for additional polymorphisms in the NAT gene region was also performed on 20 of the 26 cases. NAT2 genotype frequency between cases and controls was compared.RESULTS:
NAT2 genotypes predicting a slow acetylator phenotype were found to be associated with an increased risk of isoniazid-related liver injury (odds ratio (OR) = 4.25 (95% confidence interval (CI), 1.36-13.22); p = 0.012) with 85% of the cases being slow acetylators compared with 56% of the controls. There was no evidence for an increased risk for the slow acetylator genotype in patients with the most severe cases of liver injury, who underwent liver transplantation.CONCLUSIONS:
The NAT2 slow acetylator genotype appears to be a significant risk factor for moderate and severe drug- induced liver injury. However, the overall effect size is modest and generally in line with effects described previously for this genotype in milder drug-induced liver injury. Additional genetic risk factors may also contribute.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Arilamina N-Acetiltransferasa
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Enfermedad Hepática Inducida por Sustancias y Drogas
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Antituberculosos
Tipo de estudio:
Etiology_studies
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Observational_studies
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Prognostic_studies
/
Risk_factors_studies
Límite:
Adult
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Female
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Humans
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Male
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Middle aged
País/Región como asunto:
Asia
/
Europa
Idioma:
En
Revista:
Eur J Clin Pharmacol
Año:
2014
Tipo del documento:
Article
País de afiliación:
Reino Unido