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Lack of association between genetic polymorphisms of CYP3A4, CYP2C9, CYP2C19 and anti-tuberculosis drug-induced liver injury in community-based Chinese population.


Clin Exp Pharmacol Physiol. 2013 Mar 7;


Authors: Tang SW, Lv XZ, Chen R, Wu SS, Yang ZR, Chen DF, Zhan SY


Abstract

1 The precise pathogenic mechanism of anti-tuberculosis (anti-TB) drug-induced liver injury (ATLI) is poorly understood. It may associate with drug metabolizing enzymes such as CYP3A4, CYP2C9 and CYP2C19. The present study was aimed to explore the role of tagging single nucleotide polymorphisms (tSNPs) of CYP3A4, CYP2C9 and CYP2C19 in the risk of ATLI in a population-based anti-TB treatment cohort. 2 A nested case-control study was designed. Each ATLI case was 1:4 matched with controls by age, gender, treatment history, disease severity and drug dosage. The tSNPs were selected by using Haploview 4.2 based on the HapMap database of Han Chinese in Beijing, and genotyped by using TaqMan allelic discrimination technology. 3 Eighty-nine ATLI cases and 356 controls were included. One tSNP in CYP3A4 (rs12333983), two in CYP2C9 (rs4918758, rs9332098), two in CYP2C19 (rs11568732, rs4986894) were selected and genotyped. The minor allele frequencies of rs12333983, rs4918758, rs9332098, rs11568732 and rs4986894 were 36.0%, 41.4%, 1.1%, 5.7% and 35.7% in the cases and 31.7%, 42.9%, 3.4%, 8.9% and 35.1% in the controls, respectively. No significant differences were observed in genotypes or allele frequencies of the 5 tSNPs between two groups, and neither of haplotypes in CYP2C9 nor in CYP2C19 was significantly associated with the development of ATLI. 4 Based on the Chinese anti-TB treatment cohort, we did not find a statistically significant association between genetic polymorphisms of CYP3A4, CYP2C9, CYP2C19 and the risk of ATLI. None of the haplotypes showed a significant association with the development of ATLI in Chinese TB population. © 2013 The Authors Clinical and Experimental Pharmacology and Physiology © 2013 Wiley Publishing Asia Pty Ltd.

PMID: 23469989 [PubMed - as supplied by publisher]