title: NAT2 slow acetylator associated with anti-tuberculosis drug-induced liver injury in Thai patients.
abstract: Anti-tuberculosis drug-induced liver injury (AT-DILI) is one of the most common forms of drug-induced liver injury (DILI) in high tuberculosis (TB) burden countries. Among anti-tuberculosis drugs, isoniazid is the main cause of hepatotoxicity in patients with AT-DILI.
  
  
  
  To investigate the association of AT-DILI with N-acetyltransferase 2 (NAT2) genotype status in Thai TB patients.
  
  
  
  We enrolled 53 patients diagnosed with AT-DILI and 85 patients who tolerated anti-tuberculosis treatment as controls. Acetylator status was determined based on the inferred NAT2 haplotypes from four common single-nucleotide polymorphisms (SNPs) in Thais using Sanger sequencing.
  
  
  
  Phenotype frequencies of the NAT2 acetylator in AT-DILI patients were respectively 71.7%, 22.6% and 5.7% for slow, intermediate and rapid acetylators. Among slow, intermediate, and rapid acetylators in treatment tolerant controls, phenotype frequencies were respectively 22.4%, 62.4% and 15.3%. Slow NAT2 acetylators demonstrated a significant association with risk of AT-DILI. The odds ratio of comparing slow NAT2 acetylator in DILI patients and tolerance was 8.80 (95%CI 4.01-19.31, P = 1.53 × 10-8).
  
  
  
  Slow acetylator status in the NAT2 genotype is a significant risk factor for DILI in Thai patients with TB. This evidence provides confirmatory data in support of the role of NAT2 in AT-DILI in the Thai population.
authors.affiliation: Medical Genetics Center, Medical Life Sciences Institute, Department of Medical Sciences, Ministry of Public Health, Nonthaburi, Thailand; Department of Human Genetics, Graduate School of Medicine, University of Tokyo, Bunkyo-ku, Tokyo, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Wattanapokayakit
authors.affiliation: Laboratory for Pharmacogenomics, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Mushiroda
authors.affiliation: Fukujuji Hospital, Japan Anti-tuberculosis Association, Kiyose, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Yanai
authors.affiliation: Medical Genetics Center, Medical Life Sciences Institute, Department of Medical Sciences, Ministry of Public Health, Nonthaburi, Thailand.
authors.forename: N
authors.initials: N
authors.lastname: Wichukchinda
authors.affiliation: Central Chest Institute of Thailand, Department of Medical Services, Ministry of Public Health, Nonthaburi, Thailand.
authors.forename: C
authors.initials: C
authors.lastname: Chuchottawon
authors.affiliation: Chiangrai Prachanukroh Hospital, Department of Social and Preventive Medicine, Ministry of Public Health, Chiang Rai, Thailand.
authors.forename: S
authors.initials: S
authors.lastname: Nedsuwan
authors.affiliation: Medical Genetics Center, Medical Life Sciences Institute, Department of Medical Sciences, Ministry of Public Health, Nonthaburi, Thailand.
authors.forename: A
authors.initials: A
authors.lastname: Rojanawiwat
authors.affiliation: Chiangrai Prachanukroh Hospital, Department of Social and Preventive Medicine, Ministry of Public Health, Chiang Rai, Thailand.
authors.forename: S
authors.initials: S
authors.lastname: Denjanta
authors.affiliation: TB/HIV Research Foundation, Chiang Rai, Thailand.
authors.forename: T
authors.initials: T
authors.lastname: Kantima
authors.affiliation: TB/HIV Research Foundation, Chiang Rai, Thailand.
authors.forename: J
authors.initials: J
authors.lastname: Wongyai
authors.affiliation: Health Product Vigilance Centre, Food and Drug Administration, Ministry of Public Health, Nonthaburi, Thailand.
authors.forename: W
authors.initials: W
authors.lastname: Suwankesawong
authors.affiliation: Health Product Vigilance Centre, Food and Drug Administration, Ministry of Public Health, Nonthaburi, Thailand.
authors.forename: W
authors.initials: W
authors.lastname: Rungapiromnan
authors.affiliation: Buddhachinaraj Hospital, Phitsanulok, Thailand.
authors.forename: R
authors.initials: R
authors.lastname: Kidkeukarun
authors.affiliation: Rayong Hospital, Rayong, Thailand.
authors.forename: W
authors.initials: W
authors.lastname: Bamrungram
authors.affiliation: Maesot Hospital, Tak, Thailand.
authors.forename: A
authors.initials: A
authors.lastname: Chaiwong
authors.affiliation: Department of Human Genetics, Graduate School of Medicine, University of Tokyo, Bunkyo-ku, Tokyo, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Suvichapanich
authors.affiliation: Medical Genetics Center, Medical Life Sciences Institute, Department of Medical Sciences, Ministry of Public Health, Nonthaburi, Thailand.
authors.forename: S
authors.initials: S
authors.lastname: Mahasirimongkol
authors.affiliation: Department of Human Genetics, Graduate School of Medicine, University of Tokyo, Bunkyo-ku, Tokyo, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Tokunaga
mesh_terms: D000107:Acetylation; D000328:Adult; D000368:Aged; D000995:Antitubercular Agents / Q000008:administration & dosage / Q000009:adverse effects*; D001191:Arylamine N-Acetyltransferase / Q000235:genetics* / Q000378:metabolism; D016022:Case-Control Studies; D056486:Chemical and Drug Induced Liver Injury / Q000175:diagnosis* / Q000235:genetics; D005260:Female; D005787:Gene Frequency; D060005:Genotyping Techniques; D006239:Haplotypes; D006801:Humans; D007538:Isoniazid / Q000008:administration & dosage / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D015995:Prevalence; D012307:Risk Factors; D017422:Sequence Analysis, DNA; D013785:Thailand; D014376:Tuberculosis / Q000188:drug therapy*
chemical_list: D000995:Antitubercular Agents; D001191:Arylamine N-Acetyltransferase; C478900:NAT2 protein, human; D007538:Isoniazid