The association of CpG island DNA methylation in the promoter region, genetic polymorphism of ALAS1 with anti-tuberculosis drug-induced liver injury

Abstract Anti-tuberculosis drug-induced liver injury (AT-DILI) may be related to the accumulation of hepatotoxin protoporphyrin IX, while aminolevulinate synthase 1 (ALAS1) is the key rate-limiting enzyme. The study aimed to investigate the association of CpG island methylation, genetic polymorphism of ALAS1 with the risk of AT-DILI. Based on 1:1 matched case-control study with 150 AT-DILI cases and 150 controls, patients with methylation status were at a high risk of AT-DILI (OR = 1.784, 95%CI: 1.098–2.899, P = 0.019), and patients carrying the CT genotype of rs352169 had an increased risk of AT-DILI (OR = 1.719, 95%CI: 1.019–2.901, P = 0.043). Furthermore, patients with CT + TT genotype and methylation status had a higher risk of AT-DILI than those with CC genotype and unmethylation status (OR = 3.348, 95%CI: 1.407–7.964, P = 0.006). So, the methylation status and rs352169 polymorphism in ALAS1 may be associated with the susceptibility to AT-DILI. Moreover, there may be a synergistic effect between methylation and polymorphism in the occurrence of AT-DILI.