Abstract
Evidence indicates that the polymorphisms in bile salt export pump (BSEP, encoded by ABCB11) may play an important role in the development of anti-tuberculosis drug-induced liver injury (ATDILI) and we aim to investigate the association between genetic variants of ABCB11 and the risk of ATDILI in a Chinese cohort. A total of 89 tuberculosis patients with ATDILI and 356 matched ATDILI -free patients constituted cases and controls. Genetic polymorphisms of ABCB11 were determined by TaqMan single-nucleotide polymorphism (SNP) genotyping assay. Odds ratio (OR) with 95% confidence intervals (CIs) was estimated by conditional logistic regression model. There were no significant differences in genotype frequencies of ABCB11 between cases and controls. In the subgroup analysis, polymorphisms of rs2287616 were found to be associated with cholestatic/mixed pattern of liver injury under dominant and addictive model (OR = 3.84, 95% CI:1.16–12.75, P = 0.028 and OR = 2.51, 95% CI:1.12–5.62, P = 0.025, respectively), however the significance disappeared after Bonferroni correction. This study suggested that genetic variants of ABCB11 gene might contribute to anti-tuberculosis drug-induced cholestatic liver injury in Chinese patients. Studies in larger, varied populations are required to confirm these findings.
Highlights
As one of the most prevalent DILI, anti-tuberculosis drugs (ATDs) induced liver injury (ATDILI) is of importance due to relatively high incidence and large disease burden of tuberculosis (TB), which posed a considerable challenge to clinicians and researchers
Vitro study has demonstrated that ATDs administration significantly down-regulated the expression of bile salt export pump (BSEP) in liver[14], it is reasonable to speculate that genetic variations in ABCB11 may play a role in the development of ATDILI by altering the expression of BSEP and disturbing the transport of bile acids[15]
We investigated the association between polymorphisms of ABCB11 and the development of ATDILI among Chinese population
Summary
As one of the most prevalent DILI, anti-tuberculosis drugs (ATDs) induced liver injury (ATDILI) is of importance due to relatively high incidence and large disease burden of tuberculosis (TB), which posed a considerable challenge to clinicians and researchers. The mechanism of ATDILI is poorly understood and whether genetic variants of ABCB11 contribute to its susceptibility is seldom investigated. Vitro study has demonstrated that ATDs administration significantly down-regulated the expression of BSEP in liver[14], it is reasonable to speculate that genetic variations in ABCB11 may play a role in the development of ATDILI by altering the expression of BSEP and disturbing the transport of bile acids[15]. The present study is aimed to explore the association between ABCB11 polymorphisms and the risk of ATDILI in Chinese population
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