Genetic variations of NAT2 and CYP2E1 and isoniazid hepatotoxicity in a diverse population

Yamada, So, Tang, Mila, Richardson, Kathryn, Halaschek-Wiener, Julius, Chan, Matthew, Cook, Victoria J., Fitzgerald, J. Mark, Elwood, R. Kevin, Brooks-Wilson, Angela and Marra, Fawziah (2009) Genetic variations of NAT2 and CYP2E1 and isoniazid hepatotoxicity in a diverse population. Pharmacogenomics, 10 (9). pp. 1433-1445. ISSN 1744-8042

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Abstract

Aims: TB is a serious global public health problem. Isoniazid, a key drug used to treat latent TB, can cause hepatotoxicity in some patients. This pilot study investigated the effects of genetic variation in NAT2 and CYP2E1 on isoniazid-induced hepatotoxicity in TB contacts in British Columbia, Canada. Materials & methods: DNA re-sequencing was used to establish the spectrum of genetic variation in the exons, promoter and conserved regions of NAT2 in all subjects. For CYP2E1, the CYP2E1*1C polymorphism was genotyped by PCR-RFLP. Association tests of NAT2 variants and haplotypes, as well acetylator types were performed. Results: We enrolled 170 subjects on isoniazid treatment (23 cases and 147 controls). Systematic re-sequencing of NAT2 revealed 18 known and 10 novel variants. Conclusion: No single genetic variant of NAT2 and CYP2E1 showed a significant association with isoniazid-induced hepatotoxicity in this highly heterogeneous population. There was evidence of a trend for increasing hepatotoxicity risk across the rapid, intermediate and slow acetylator groups (p = 0.08).

Item Type:	Article
Additional Information:	A Corrigendum has been published for this article:: The CYP2E1 polymorphism studied was erroneously identified as CYP2E1*1C. This variant was actually the CYP2E1*5 polymorphism (rs2031920) that is detected by means of an RsaI PCR-RFLP. The authors would like to sincerely apologize for any inconvenience caused. [Corrigendum. (2010). Pharmacogenomics, 11(9), 1343. https://doi.org/10.2217/pgs.10.114].
Faculty \ School:	Faculty of Medicine and Health Sciences > School of Health Sciences
UEA Research Groups:	Faculty of Medicine and Health Sciences > Research Groups > Health Promotion Faculty of Science > Research Groups > Norwich Epidemiology Centre Faculty of Medicine and Health Sciences > Research Groups > Norwich Epidemiology Centre
Depositing User:	Pure Connector
Date Deposited:	05 Jan 2015 15:04
Last Modified:	12 Aug 2025 08:30
URI:	https://ueaeprints.uea.ac.uk/id/eprint/51639
DOI:	10.2217/pgs.09.66

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