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Table 1 Summary of findings of previously conducted meta-analyses

From: Influence of genetic variants on toxicity to anti-tubercular agents: a systematic review and meta-analysis (protocol)

Review Findings
NAT2 gene CYP2E1 gene GSTM1 gene GSTT1 gene
Cai et al. (2012) [27] Slow NAT2 genotype (without wild-type NAT2*4 allele) significantly increases the risk of ATDILI CYP2E1 c1/c1 genotype significantly increases the risk of ATDILI among East Asian patients. This result is non-significant for the wider population GSTM1 null genotype significantly increases risk of ATDILI GSTT1 null genotype has no effect on ATDILI risk
Cai et al. (2015) [31] The GSTM1 present genotype is significantly associated with decreased risks of ATDILI and schizophrenia The GSTT1 present genotype is significantly associated with a high risk of schizophrenia, but not with ATDILI according to the fixed-effect model
Deng et al. (2012) [32] CYP2E1 c1/c1 genotype significantly increases the risk of ATDILI. When stratifying for study population, significant results are observed in Chinese and Korean populations
Du et al. (2013) [33] Slow acetylator genotype of NAT2 (without wild-type NAT2*4 allele) significantly increases risk of ATDH. When stratifying for study population, this result is significant for East Asian, South Asian, Brazilian and Middle Eastern populations, but not for Caucasian populations
Li et al. (2013) [34] ATDH risk is significantly increased in GSTM1 null genotypes. Subgroup analyses show that the association is significant in patients receiving HRZE or HRZES, and East Asians. The opposite result is observed for patients treated with HR The GSTT1 polymorphism is not associated with ATDH risk, except in patients receiving HRZ
Sheng et al. (2014) [35] CYP2E1 c1/c1 genotype significantly increases risk of ATDH. CYP2E1 D/D genotype is not significantly associated with ATDH. CYP2E1 c1/c1 genotype patients who are NAT2 slow acetylators have significantly higher risk of ATDH than CYP2E1 c1/c1 genotype patients who are NAT2 fast or intermediate acetylators
Shi et al. (2015)[36] Slow acetylator status is associated with increased risk of ATDILI compared with fast and intermediate acetylators when standard dose of isoniazid is administered
Sun et al. (2008) [25] Slow NAT2 genotype (without wild-type NAT2*4 allele) does not significantly increase risk of ATDILI. A significant effect is demonstrated among Asian populations CYP2E1 c1/c1 genotype is significantly associated with an increased risk of ATDILI GSTM1 null genotype significantly increases risk of ATDILI GSTT1 null genotype has no effect on ATDILI risk
Tang et al. (2013) [37] GSTM1 null genotype is significantly associated with increased risk of ATDILI. Stratified analyses demonstrate significant associations in Chinese populations and when restricting to studies with case numbers >57 No statistically significant association is observed between GSTT1 null genotype, or GSTM1/GSTT1 interaction and risk of ATDILI
Wang et al. (2012) [28] Individuals homozygous for rapid NAT2 acetylator alleles (NAT2*4, NAT2*11A, NAT2*12A, NAT2*12B, NAT2*12C, NAT2*13) are rapid acetylators; individuals homozygous for slow acetylator alleles are slow acetylators, and heterozygous individuals are intermediate acetylators. Slow acetylators have significantly higher risk of ATDILI than other acetylators
Wang et al. 2016 [38] CYP2E1 c1/c1 genotype is significantly associated with an increased risk of ATDH. CYP2E1 D/D genotype is not significantly associated with ATDH. When stratifying for study population, significant results are observed in East Asian populations only
  1. ATDH anti-tuberculosis drug-induced hepatotoxicity, ATDILI anti-tuberculosis drug-induced liver injury, H isoniazid, R rifampicin, Z pyrazinamide, E ethambutol, S streptomycin