Association of ABCG2 polymorphisms with susceptibility to anti-tuberculosis drug-induced hepatotoxicity in the Chinese population

Abstract

The accumulation of endogenous hepatotoxin protoporphyrin IX (PPIX) in the liver was proposed to be a novel mechanism of anti-tuberculosis drug-induced hepatotoxicity (ATDH). ATP-binding cassette transporter G2 (ABCG2) plays an important role in modulating PPIX concentrations. This study aimed to explore the role of ABCG2 genetic polymorphisms in the risk of ATDH in Chinese patients. A 1:4 matched case–control study was performed among 202 ATDH cases and 808 controls. Conditional logistic regression model was used to estimate the association between genotypes and the risk of ATDH by odds ratios (ORs) with 95% confidence intervals (CIs). Male patients with CC genotype of rs2622605 had an increased risk of ATDH (adjusted OR = 1.615, 95% CI: 1.119–2.332, p = 0.011). The peak value of alkaline phosphatase (ALP) was significantly higher in male patients with CC genotype of rs2622605 than in those with TT + TC genotype during antituberculosis treatment (102.0 U/L vs. 98.0 U/L, p = 0.029). This is the first attempt to evaluate the association between ABCG2 genetic variants and the risk of ATDH. Based on the 1:4 matched case–control study, the polymorphism at rs2622605 in the ABCG2 gene may be associated with the susceptibility to ATDH in Chinese male patients.