NAT2*6A,a haplotype of the N-acetyltransferase 2 gene, is an important biomarker for risk of anti-tu

• 作 者: Norihide Higuchi Naoko Tahara
• 机 构: Department of Pharmacotherapeutics,Second Department of Internal Medicine,Division of Internal Medic
• 出 处: 世界胃肠病学杂志
• 发表日期: 2004年期
• 关键词: Tuberculosis Anti-tuberculosis drugs Druginduced hepatotoxicity NAT2-haplotype D

AIM: To investigate an association between N-acetyltransferase 2 (NAT2)-haplotypes/diplotypes and adverse effects in apanese pulmonary tuberculosis patients.METHODS: We studied 100 patients with pulmonary TB treated with anti-TB drugs including INH. The frequencies and distributions of single nucleotide polymorphisms, haplotypes, and diplotypes of NAT2 were determined by the PCR-restriction fragment length polymorphism method, and the results were compared between TB patients with and without adverse effect,using multivariate logistic regression analysis.RESULTS: Statistical analysis revealed that the frequency of a variant haplotype, NAT2*6A, was significantly increased in TB patients with hepatotoxicity,compared with those without hepatotoxicity [P = 0.001,odds ratio (OR) = 3.535]. By contrast, the frequency of a wild-type (major) haplotype,"NAT2*4″, was significantly lower in TB patients with hepatotoxicity than those without hepatotoxicity (P ＜ 0.001, OR = 0.265).There was no association between NAT2-haplotypes and skin rash or eosinophilia.CONCLUSION: The present study shows that NAT2 is one of the determinants of anti-TB drug-induced hepatotoxicity. Moreover, the haplotypes, NAT2*4 and NAT2*6A, are useful new biomarkers for predicting antiTB drug-induced hepatotoxicity.