The relevance of ABC transporters to drug-induced liver injury is also considered, together with data showing associations of particular ABCB11, ABCB1 and ABCC2 polymorphisms with some forms of drug-induced liver injury.
We found that rs12422149 of SLCO2B1, rs2032582_AT of ABCB1, rs2306283 of SLCO1B1 and rs4148323 of UGT1A1 exhibited a significant association with MMI-DILI; however, no significant difference existed after Bonferroni correction.
Homozygosity for GSTM1 null and/or GSTT1 null alleles also seems to be a risk factor for DILI, with associations described independently for several drugs.
Subset analysis of NAT2 acetylator status and severity grade confirmed these results in AT-DILI patients with more severe disease whereas fast and intermediate acetylator phenotypes were associated with a decreased AT-DILI risk.
Two SNPs in NAT2 (rs1041983 and rs1495741) and NAT2 slow acetylators (SA) were significantly associated with INH-DILI (OR (95% CI) = 13.86 (4.30-44.70), 0.10 (0.03-0.33) and 9.98 (3.32-33.80), respectively).
As a result, the ABCC2 rs3740065 genotype, sex, and the baseline level of alanine aminotransferase are independent risk factors of antituberculosis drug-induced hepatotoxicity, with P values of .008, .014, and <.001, respectively.
The aim of this study is to evaluate the potential association between N-acetyltransferase type 2 (NAT2) polymorphisms and drug-induced liver injury during anti-TB treatment (AT-DILI).
No significant association was observed between the GSTM1 homozygous null polymorphism and antituberculosis drug-induced hepatotoxicity (OR 0.73, 95% CI 0.31-1.73, P=0.48).
Update meta-analysis of the CYP2E1 RsaI/PstI and DraI polymorphisms and risk of antituberculosis drug-induced hepatotoxicity: evidence from 26 studies.
Previous studies suggest that individuals who are homozygous-null at the GSTM1 or GSTT1 locus may have an increased risk of environmentally related cancers and drug-induced hepatotoxicity.
Although acute DILI has been linked to specific genetic associations (e.g., flucloxacillin and HLA-B*5701; and certain polymorphisms seen with anti-TB agent DILI), such predictors have been able to identify only some patients at risk for only a limited number of drugs.
In conclusion, this study confirms the significance of the association between slow-acetylator NAT2 variants and susceptibility to AT-DILI in an Indonesian population.