Lookup NU author(s): Ching Ng,
Dr Abul Hasnat,
Professor Chris Day,
Professor Ann Daly
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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.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.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.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.
Author(s): Ng CS, Hasnat A, Al Maruf A, Ahmed MU, Pirmohamed M, Day CP, Aithal GP, Daly AK
Publication type: Article
Publication status: Published
Journal: European Journal of Clinical Pharmacology
Print publication date: 01/09/2014
Online publication date: 03/06/2014
Acceptance date: 22/05/2014
ISSN (print): 0031-6970
ISSN (electronic): 1432-1041
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