title: The NAT2 tag SNP rs1495741 correlates with the susceptibility of antituberculosis drug-induced hepatotoxicity.
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.
  
  
  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).
  
  
  CONCLUSIONS
  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.
authors: Graduate Institute of Life Sciences, Tri-Service General Hospital, College of Medicine, Kaohsiung Medical University, Taiwan, ROC.
authors: Hsin-Tien
authors: HT
authors: Ho
authors: Teng-Hsu
authors: TH
authors: Wang
authors: Cheng-Huei
authors: CH
authors: Hsiong
authors: Wann-Cherng
authors: WC
authors: Perng
authors: Ning-Chi
authors: NC
authors: Wang
authors: Tien-Yu
authors: TY
authors: Huang
authors: Yuh-Jyh
authors: YJ
authors: Jong
authors: Po-Liang
authors: PL
authors: Lu
authors: Oliver Yoa-Pu
authors: OY
authors: Hu
mesh_terms: D000328:Adult; D000368:Aged; D000483:Alleles; D000995:Antitubercular Agents / Q000008:administration & dosage / Q000009:adverse effects; D001191:Arylamine N-Acetyltransferase / Q000235:genetics*; D056486:Chemical and Drug Induced Liver Injury / Q000150:complications / Q000235:genetics*; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D007538:Isoniazid / Q000008:administration & dosage / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D014376:Tuberculosis / Q000150:complications / Q000188:drug therapy* / Q000473:pathology
chemical_list: D000995:Antitubercular Agents; D001191:Arylamine N-Acetyltransferase; C478900:NAT2 protein, human; D007538:Isoniazid