Cytochrome P450 2E1 (CYP2E1) plays a vital role in drug-induced hepatotoxicity and cancers (e.g. lung and bladder cancer), since it is responsible for metabolizing a number of medications and environmental toxins to reactive intermediate metabolites.
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).
RUCAM criteria were defined as the gold standard, and the other two criteria were as follows: 1) ALT or aspartate aminotransferase (AST) levels greater than 5 × the ULN on two consecutive occasions and/or ALP levels greater than 2 × the ULN on two consecutive occasions [issued by DILI Network (DILIN)]; 2) ALT levels greater than 1 × the ULN on two consecutive occasions or ALT levels greater than 2 × the ULN [issued by the National Medical Products Administration (NMPA) of China].
We found no HLA-B*57 association with DILI due to other isoxazolyl penicillins (n = 6) or amoxicillin (n = 15) and no significant non-HLA signals for any penicillin-relatedDILI.
Update meta-analysis of the CYP2E1 RsaI/PstI and DraI polymorphisms and risk of antituberculosis drug-induced hepatotoxicity: evidence from 26 studies.
Identification of genetic predispositions to DILI is coming of age with the FDA calling for the testing of human leukocyte antigen B(*)5701 before the use of abacavir to reduce the risk of hypersensitivity reactions.
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.
The double-null genotype for GSTT1 and GSTM1 might play a role in determining the susceptibility to develop DILI, as a general mechanism that occurs regardless of the type of drug involved, and predominantly in women.
A significant association was noted between HLA-B∗35:02 and risk for minocycline DILI; a 16% carrier frequency in DILI cases compared to 0.6% in population controls (odds ratio: 29.6, 95% CI: 7.8-89.8, p=2.5×10<sup>-8</sup>).
Conclusion: GLDH appears to be more useful than miR-122 in identifying DILI patients, and K18, OPN, and MCSFR are promising candidates for prediction of prognosis during an acute DILI event.