NAT2 slow acetylator associated with anti-tuberculosis drug-induced liver injury in Thai patients
| Autor: | S, Wattanapokayakit, T, Mushiroda, H, Yanai, N, Wichukchinda, C, Chuchottawon, S, Nedsuwan, A, Rojanawiwat, S, Denjanta, T, Kantima, J, Wongyai, W, Suwankesawong, W, Rungapiromnan, R, Kidkeukarun, W, Bamrungram, A, Chaiwong, S, Suvichapanich, S, Mahasirimongkol, K, Tokunaga |
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| Rok vydání: | 2016 |
| Předmět: |
Adult
Male Genotyping Techniques Arylamine N-Acetyltransferase Antitubercular Agents Acetylation Sequence Analysis DNA Middle Aged Thailand Polymorphism Single Nucleotide Gene Frequency Haplotypes Risk Factors Case-Control Studies Isoniazid Prevalence Humans Tuberculosis Female Chemical and Drug Induced Liver Injury Aged |
| Zdroj: | The international journal of tuberculosis and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease. 20(10) |
| ISSN: | 1815-7920 |
| Popis: | 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 × 10Slow 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. |
| Databáze: | OpenAIRE |
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