Genetic Polymorphisms of UDP-Glucuronosyltransferases and Susceptibility to Antituberculosis Drug-Induced Liver Injury: A Systematic Review and Meta-Analysis

Abstract

Background and Aim. UDP-glucuronosyltransferases (UGTs) play an important role in drug metabolism and detoxification by catalyzing the glucuronidation reaction, which is associated with the occurrence of antituberculosis drug-induced liver injury (AT-DILI). The relationship between UGTs polymorphisms and AT-DILI risk has been reported but with inconsistent results. We conducted a systematic review and meta-analysis to summarize the previous study results and evaluate the precise relationships. Methods. The PRISMA statement was strictly followed, and the protocol was registered in PROSPERO (CRD42022339317). The PICOS framework was used: patients received antituberculosis treatment, UGTs polymorphisms (mutants), UGTs polymorphisms (wild), AT-DILI, and case-control studies. Eligible studies were searched through nine databases up to April 27, 2022. The study’s qualities were assessed by the revised Little’s recommendations. Meta-analysis was conducted with a random-effects model using odds ratios (ORs) with 95% confidence intervals (95% CIs) as the effect size. Results. Twelve case-control studies with 2128 cases and 4338 controls were included, and 32 single nucleotide polymorphisms (SNPs) in the seven UGT genes have been reported in Chinese and Korean. All studies were judged as high quality. The pooled results indicated that UGT1A1 rs3755319 (AC vs. AA, OR = 1.454, 95% CI: 1.100–1.921, $P$  = 0.009), UGT2B7 rs7662029 (G vs. A, OR = 1.547, 95% CI: 1.249–1.917, $P$  < 0.0001; GG + AG vs. AA, OR = 2.371, 95% CI: 1.779–3.160, $P$  < 0.0001; AG vs. AA, OR = 2.686, 95% CI: 1.988–3.627, $P$  < 0.0001), and UGT2B7 rs7439366 (C vs. T, OR = 0.585, 95% CI: 0.477–0.717, $P$  < 0.0001; CC + TC vs. TT, OR = 0.347, 95% CI: 0.238–0.506, $P$  < 0.0001; CC vs. TC + TT, OR = 0.675, 95% CI: 0.507–0.898, $P$  = 0.007) might be associated with the risk of AT-DILI. Conclusions. The polymorphisms of UGT1A1 rs3755319, UGT2B7 rs7662029, and UGT2B7 rs7439366 were significantly associated with AT-DILI susceptibility. However, this conclusion should be interpreted with caution due to the low number of studies and the relatively small sample size.