NAT2＊6A, a haplotype of the N-acetyltransferase 2 gene, is an important biomarker for risk of anti-tuberculosis drug-induced hepatotoxicity in Japanese patients with tuberculosis

作     者：Norihide Higuchi Naoko Tahara Katsunori Yanagihara Kiyoyasu Fukushima Naofumi Suyama Yuichi Inoue Yoshitsugu Miyazaki Tsutomu Kobayashi Koh-ichiro Yoshiura Norio Niikawa, Chun-Yang Wen, Hajime Isomoto,Saburou Shikuwa, Katsuhisa Omagari, Yohei Mizuta, Shigeru Kohno, Kazuhiro Tsukamoto Norio Niikawa Chun-Yang Wen Hajime Isomoto Saburou Shikuwa Katsuhisa Omagari Yohei Mizuta Shigeru Kohno Kazuhiro Tsukamoto 

作者机构：Department of Pharmacotherapeutics Nagasaki University Graduate School of Biomedical Sciences 1-14 Bunkyo-machi Nagasaki 852-8521 Japan Department of Internal Medicine Nagasaki University Graduate School of Biomedical Sciences Sakamoto 1-7-1 Nagasaki 852-8501 Japan Division of Internal Medicine Japanese Red Cross Nagasaki Genbaku Isahaya Hospital Isahaya 859-0497 Japan Department of Internal Medicine Nagasaki Municipal Medical Center Nagasaki 852-8012 Japan Y Department of Internal Medicine Isahaya Health Insurance General Hospital Isahaya 854-8501 Japan Department of Human Genetics Nagasaki University Graduate School of Biomedical Sciences Sakamoto 1-12-4 Nagasaki 852-8523 Japan SORST JST Kawaguchi Japan Department of Digestive Disease Center Beihua University Jilin 132013 Jilin Province China 

出 版 物：《World Journal of Gastroenterology》 (世界胃肠病学杂志（英文版）)

年 卷 期：2007年第13卷第45期

页      面：6003-6008页

核心收录：

学科分类：1002[医学-临床医学] 100201[医学-内科学(含：心血管病、血液病、呼吸系病、消化系病、内分泌与代谢病、肾病、风湿病、传染病)] 10[医学] 

基　　金：by Grant-in-Aid for Scientif ic Research (Category B  No. 18390168) for K Tsukamoto by the Ministry of Education  Culture  Sports  Science and Technology of Japan 

主　　题：Tuberculosis Anti-tuberculosis drugs Drug-induced hepatotoxicity NAT2-haplotype DNA-baseddiagnosis 

摘      要：AIM: To investigate an association between N -acetyltransferase 2 (NAT2 )-haplotypes/diplotypes and adverse effects in Japanese 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 ***: Statistical analysis revealed that the frequency of a variant haplotype, NAT2*6A , was signifi cantly 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 signif icantly 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 anti- TB drug-induced hepatotoxicity.