TABLE 2.
Examples of genes putatively associated with isoniazid-induced hepatotoxicitya
| Gene | Genetic polymorphisms | Possible results |
|---|---|---|
| NAT2 | NAT2 *2, *5, *6, *7 | Risk of hepatotoxicity |
| CYP2E1 | CYP2E1*1A,*5,*6 | Risk of hepatotoxicity |
| GSTb | GSTM1, GSTT1 null homozygous | Risk of hepatotoxicity |
| UGT1A | TA insertion in gene promoter | Risk of hyperbilirubinemia and hepatotoxicity |
| HLA | HLA-DQ | Risk of hepatotoxicity |
| NOS | NOS2A (inducible isoform) | Risk of hepatotoxicity |
| BACHb | BACH1 CC genotype at rs11080344 | Risk of hepatotoxicity |
| MAFKb | Homozygous mutant genotype at rs4720833 | Risk of hepatotoxicity |
| MnSODb | Homozygous/heterozygous mutant C allele (T/C or C/C) | Risk of hepatotoxicity |
| ABCB11c | T→C V444A | Risk of hyperbilirubinemia and hepatotoxicity? |
| ABCB4c | Various transversions | |
| ABCC2c | Various transversions | |
| SLCO1B1c | T→C V174A | Risk of hepatotoxicity? |
a
ABCB4, ATP binding cassette superfamily B member 4; ABCB11, ATP binding cassette superfamily B member 11; ABCC2, ATP binding cassette superfamily C member 2; BACH, BTB and CNC homolog basic leucine zipper transcription factor; HLA, human leukocyte antigen; MAFK, Maf basic leucine zipper protein; MnSOD, manganese superoxide dismutase; NOS, nitric oxide synthase; SLCO1B1, solute carrier organic anion transporter family member 1B1; UGT, UDP glucuronosyltransferase.
b
Associated with antioxidative defense.
c
May contribute to interactive hepatotoxicity of rifampin and isoniazid.