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Lack of association between genetic polymorphisms of CYP 3A4 , CYP 2C9 and CYP 2C19 and antituberculosis drug‐induced liver injury in a community‐based Chinese population
Author(s) -
Tang ShaoWen,
Lv XiaoZhen,
Chen Ru,
Wu ShanShan,
Yang ZhiRong,
Chen DaFang,
Zhan SiYan
Publication year - 2013
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1111/1440-1681.12074
Subject(s) - single nucleotide polymorphism , minor allele frequency , snp , genotype , biology , cytochrome p450 , haplotype , nested case control study , cyp2c19 , pharmacology , medicine , genetics , case control study , endocrinology , gene , metabolism
Summary The precise pathogenic mechanism of antituberculosis (anti‐TB) drug‐induced liver injury ( ATLI ) is poorly understood. It may be associated with drug‐metabolizing enzymes, such as cytochrome P450 ( CYP ) 3A4, CYP 2C9 and CYP 2C19. The aim of the present study was to explore the role of tagging single nucleotide polymorphisms (t SNP s) of CYP 3A4 , CYP 2C9 and CYP 2C19 in the risk of ATLI in a population‐based anti‐TB treatment cohort. A nested case–control study was designed. Each ATLI case was matched 1 : 4 with controls on the basis of age, gender, treatment history, disease severity and drug dosage. The t SNP s were selected using Haploview 4.2 based on the HapMap database of Han Chinese in Beijing and genotyped by TaqMan allelic discrimination technology. Eighty‐nine patients with ATLI and 356 controls were included in the study. One t SNP in CYP 3A4 (rs12333983), two in CYP 2C9 (rs4918758, rs9332098) and two in CYP 2C19 (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%, respectively, in the patients, compared with 31.7%, 42.9%, 3.4%, 8.9% and 35.1%, respectively, in the controls. No significant differences were observed in genotypes or allele frequencies of the five t SNP s between the two groups and none of the CYP 2C9 or CYP 2C19 haplotypes was significantly associated with the development of ATLI . Based on the Chinese anti‐ TB treatment cohort, we did not find a significant association between the risk of ATLI and genetic polymorphisms of CYP 3A4 , CYP 2C9 and CYP 2C19 . None of the haplotypes exhibited a significant association with the development of ATLI in a Chinese tuberculosis population.