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Free Content NAT2 and CYP2E1 polymorphisms and susceptibility to first-line anti-tuberculosis drug-induced hepatitis

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BACKGROUND: Most cases with anti-tuberculosis drug-induced hepatotoxicity (ATDH) have been attributed to isoniazid.

OBJECTIVE: To evaluate whether the polymorphisms of the cytochrome P450 2EI (CYP2E1) and N-acetyltransferase 2 (NAT2) gene are associated with ATDH.

DESIGN: A total of 140 tuberculosis (TB) patients without liver diseases before treatment who received anti-tuberculosis treatment were followed prospectively. Their CYP2E1 and NAT2 genotypes were determined using the TaqMan polymerase chain reaction assay.

RESULTS: Forty-five (32.1%) patients were diagnosed with ATDH. No significant differences were reported in age and sex between patients with and without ATDH. Slow acetylators defined by NAT2 genotypes had a higher risk of hepatotoxicity than rapid acetylators (51.2% vs. 25.2%, P = 0.0026). Odds ratio (OR) analysis showed that slow acetylator status (OR 3.15, 95%CI 1.47–6.48) was the only independent risk factor for ATDH. Pyrazinamide co-administration induced hepatitis was also associated with NAT2 acetylator status. CYP2E1 c1/c1 homozygotes are prone to developing more severe hepatotoxicity than other c1/c2 and c2/c2 genotypes.

CONCLUSION: The slow acetylator status of NAT2 is a significant susceptibility risk factor for ATDH. CYP2E1 is associated with the severity of ATDH.
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Keywords: ATDH; CYP2E1; NAT2; anti-tuberculosis drug-induced hepatitis

Document Type: Regular Paper

Affiliations: 1: Chest Medicine Department of Internal Medicine, Taoyuan General Hospital, Taoyuan, Taiwan 2: Research Development Division, Vita Genomics Inc, Taipei, Taiwan 3: Research Development Division, Vita Genomics Inc, Taipei, Taiwan; and Institute of Medical Sciences, Tzu Chi University, Hualien, Taiwan

Publication date: May 1, 2010

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  • The International Journal of Tuberculosis and Lung Disease publishes articles on all aspects of lung health, including public health-related issues such as training programmes, cost-benefit analysis, legislation, epidemiology, intervention studies and health systems research. The IJTLD is dedicated to the continuing education of physicians and health personnel and the dissemination of information on lung health world-wide.

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