Review Article

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

Table 1

Characteristics of the included studies.

GenesStudy IDCountriesStudy designMale (%)Mean age (case/control)Sample size (cases/controls)Causality assessmentDiagnostic criteriaSNPsGenotyping methodsAdjusted covariatesTreatment regimen used

UGT1A1Kim 2009KoreaMatched case-control studya65.542.1/42.867/159NR>2 ULNrs3755319, rs2003569, rs4148323SNP-ITAge, sex, baseline serum AST and ALTHRZE
UGT1A1Chang 2012China, TaiwanCase-control study67.360.4/53.417/81NR>2 ULNrs4148323, rs35350960, rs8175347, rs34946978PCR-RFLPNRHRZE
UGT1A1Chen 2016China1 : 4 matched case-control studyb73.043.7/43.689/356WHO-UMC>2 ULNrs4148323, rs8330TaqManWeight, hepatoprotectant useHRZE(S)
UGT1A1Sun 2017China1 : 1 matched case-control studya61.538.2/38.9461/466RUCAM>5 ULNrs4148323, rs4148326, rs4148328, rs12479045SNPscanNRHRZE
UGT1A1Tao 2018China1 : 2 matched case-control studyb75.547.5/47.5290/580RUCAM>2 ULNrs2003569, rs887829, rs8330, rs3755319, rs4148328, rs11563250, rs4148323, rs6719561, rs4148329Sequenom MassARRAYWeight, hepatoprotectant useHRZE(S)
UGT1A3Kim 2009KoreaMatched case-control studya65.542.1/42.867/159NR>2 ULNrs2008584, rs6431625SNP-ITAge, sex, baseline serum AST and ALTHRZE
UGT1A4Zhu 2021China1 : 4 matched case-control studyc72.349.4/50.3202/808RUCAM>2 ULNrs2011404Sequenom Mass arraySmoking, drinking, hepatoprotectant use, liver diseasesHRZE(S)
UGT1A6Hao 2011ChinaCase-control study80.047.1/45.0202/239NR>2 ULNrs6759892, 308C/A, rs2070959PCR-RFLPSmoking, drinking2HRZS(E)/4HR
UGT1A7Hao 2012ChinaCase-control study80.047.1/45.0202/239NR>2 ULNrs17868323, rs17868324, rs11692021PCR-RFLPSmoking, drinking2HRZS(E)/4HR
UGT2B4Chen 2021ChinaCase-control study59.649.4/50.3118/628NR>2 ULNrs1131878, rs1966151, rs28361541, rs4557343, rs79407331iMLDRNR2HRZE/4HR
UGT2B7Shi 2014ChinaCase-control study70.746.7/44.8182/193NR>2 ULNrs7662029, rs7439366PCR-RFLPSmoking, drinkingNR
UGT2B7Sun 2017China1 : 1 matched case-control studydNRNR207/207NR>3 ULNrs7662029, rs7439366PCR-RFLPNR2HRZS(E)/4HR
UGT2B7Chen 2017ChinaCase-control study39.732.8/38.924/223NR>2 ULNrs10028494, rs7668282Sequenom Mass arrayAge, sex, BMI, smoking2HRZE/4HR

NR, not report; PCR-RFLP, polymerase chain reaction and restriction fragment length polymorphism; WHO-UMC, World Health Organization-Uppsala Monitoring Centre system; RUCAM, Roussel Uclaf causality assessment method; SNPs, single nucleotide polymorphisms; AST, aspartate aminotransferase; ALT, alanine aminotransferase; ULN, upper limit of normal; H, isoniazid; R, rifampicin; E, ethambutol; Z, pyrazinamide; S, streptomycin. aMatched with age and sex. bMatched with age (±5 years), sex, treatment history, disease severity, drug dosage, and place. cMatched with age (±5 years), sex, and treatment history. dMatched with sex and place.