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.

Abstract

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 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 anti-TB drug-induced hepatotoxicity.

• Authors: Norihide Higuchi, Naoko Tahara, Katsunori Yanagihara, Kiyoyasu Fukushima, Naofumi Suyama, Yuichi Inoue, Yoshitsugu Miyazaki, Tsutomu Kobayashi, Kohichiro Yoshiura, Norio Niikawa, Chun-Yang Wen, Hajime Isomoto, Saburou Shikuwa, Katsuhisa Omagari, Yohei Mizuta, Shigeru Kohno, Kazuhiro Tsukamoto
• Journal: World journal of gastroenterology (World J Gastroenterol) Vol. 13 Issue 45 Pg. 6003-8 (Dec 07 2007) ISSN: 1007-9327 [Print] United States
• PMID: 18023090 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antitubercular Agents
• Arylamine N-Acetyltransferase
• NAT2 protein, human

Topics

• Adult
• Aged
• Aged, 80 and over
• Antitubercular Agents (adverse effects)
• Arylamine N-Acetyltransferase (genetics)
• Asian People
• Chemical and Drug Induced Liver Injury (genetics)
• Female
• Haplotypes
• Humans
• Japan
• Male
• Middle Aged
• Polymorphism, Restriction Fragment Length
• Polymorphism, Single Nucleotide
• Tuberculosis (drug therapy)