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N-acetyltransferase 2 polymorphisms and risk of anti-tuberculosis drug-induced hepatotoxicity in Caucasians

Leiro Fernández, Virginia; Valverde, D.; Vázquez Gallardo, Eladio Rafael; Botana Rial, María Isabel; Constenla Caramés, Lucia; Agundez, J. A.; Fernández Villar, José Alberto
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URI: http://hdl.handle.net/20.500.11940/6566
PMID: 22283902
DOI: 10.5588/ijtld.10.0648
ISSN: 1027-3719
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Int J Tuberc Lung Dis . 2011 Oct;15(10):1403-8. doi: 10.5588/ijtld.10.0648. (424.8Kb)
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Fecha de publicación
2011
Título de revista
INTERNATIONAL JOURNAL OF TUBERCULOSIS AND LUNG DISEASE
Tipo de contenido
Artigo
MeSH
Adult | Antitubercular Agents | Arylamine N-Acetyltransferase | Case-Control Studies | Chemical and Drug Induced Liver Injury | Chi-Square Distribution | European Continental Ancestry Group | Female | Gene Frequency | Genetic Predisposition to Disease | Haplotypes | Humans | Isoniazid | Logistic Models | Male | Middle Aged | Odds Ratio | Phenotype | Polymorphism, Genetic | Pyrazinamide | Rifampin | Risk Assessment | Risk Factors | Tuberculosis
Resumen
OBJECTIVE: To analyse slow-acetylation N-acetyltransferase 2 (NAT2) polymorphisms for their association with the risk of anti-tuberculosis drug-induced hepatotoxicity (ATDH). DESIGN: A case-control study including Caucasian patients with tuberculosis (TB) treated with isoniazid, rifampicin and pyrazinamide. NAT2 genotype results were compared between ATDH cases and controls and with a healthy Spanish control population of Caucasian origin. RESULTS: Fifty cases and 67 controls were included in the study. Slow, intermediate and rapid NAT2 genotypes were found in respectively 72%, 18% and 10% of cases compared with 65.7%, 25.4% and 9% of controls (P> 0.05). On comparing NAT2 genotypes among cases with those among healthy controls (n = 1312), we found more slow NAT2 genotypes and fewer intermediate genotypes among cases (respectively 72% and 18% in cases vs. 54.8% and 38.1% in controls; OR 2.07, 95%CI 1.12-2.79, P = 0.016 and OR 0.37, 95%CI 0.18-0.75, P = 0.003). CONCLUSIONS: We could not demonstrate an increased risk of ATDH related to the presence of slow NAT2 polymorphisms among this Caucasian TB cohort. However, we found a significantly greater frequency of slow and a significantly lower frequency of intermediate NAT2 genotypes among the ATDH cases compared with the healthy control population.

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