The NAT2 tag SNP rs1495741 correlates with the susceptibility of antituberculosis drug-induced hepatotoxicity

Hsin Tien Ho, Teng Hsu Wang, Cheng Huei Hsiong, Wann Cherng Perng, Ning Chi Wang, Tien Yu Huang, Yuh Jyh Jong, Po Liang Lu, Oliver Yoa Pu Hu

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17 Citations (Scopus)

Abstract

BACKGROUND: Earlier studies have demonstrated an association between N-acetyltransferase 2 (NAT2) catalytic activity and the genotype of a recently published tag single nucleotide polymorphism (SNP), rs1495741. There have been no reports on the relationship between the rs1495741 genotype and antituberculosis drug-induced hepatotoxicity (ATDIH) to date. OBJECTIVE: The aim of the present study was to determine the frequency of the NAT2 tag SNP (rs1495741) in the Taiwanese and its relation to the incidence of ATDIH. MATERIALS AND METHODS: A total of 348 tuberculosis patients were enrolled to determine the frequency of NAT2 tag SNP rs1495741 and its relation to the incidence of ATDIH. The conventional NAT2 variants alleles have also been investigated. Furthermore, to evaluate the correlation of NAT2 activity and rs1495741 genotypes, a pharmacokinetic study of isoniazid was also conducted in healthy volunteers. RESULTS: Among the 348 tuberculosis patients, 20 (5.7%) were diagnosed with ATDIH. The frequencies of the three rs1495741 genotypes, viz., AA, AG, and GG, were 24.7, 52.3, and 23.0%, respectively. Signi&filig;cant differences among rs1495741 genotypes and susceptibility to hepatotoxicity were noted (odds ratio=14.068, P<0.05). Moreover, the rs1495741 genotypes showed an association with the isoniazid dosage required for induction of hepatotoxicity. In the pharmacokinetic study, NAT2 activity was strongly associated with genotype categories (P<0.001). CONCLUSION: The present study demonstrated that the three genotypes according to rs1495741 were in good accordance with conventional NAT2 alleles-inferred phenotypes and the tag SNP could be used as a proxy to determine the susceptibility to ATDIH.

Original languageEnglish
Pages (from-to)200-207
Number of pages8
JournalPharmacogenetics and Genomics
Volume23
Issue number4
DOIs
Publication statusPublished - Apr 1 2013
Externally publishedYes

Keywords

  • hepatotoxicity
  • isoniazid
  • N-acetyltransferase
  • pharmacokinetics
  • tuberculosis

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Genetics
  • Genetics(clinical)

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  • Cite this

    Ho, H. T., Wang, T. H., Hsiong, C. H., Perng, W. C., Wang, N. C., Huang, T. Y., Jong, Y. J., Lu, P. L., & Hu, O. Y. P. (2013). The NAT2 tag SNP rs1495741 correlates with the susceptibility of antituberculosis drug-induced hepatotoxicity. Pharmacogenetics and Genomics, 23(4), 200-207. https://doi.org/10.1097/FPC.0b013e32835e95e1