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Published on: February 3, 2012
NAT2 and CYP2E1 polymorphisms and susceptibility to first-line anti-tuberculosis drug-induced hepatitis
S-W Lee1, L S-C Chung, H-H Huang
1Chest Medicine, Department of Internal Medicine, Taoyuan General Hospital, Taoyuan, Taiwan.
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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