Interestingly, HLA-B*57:01 is associated with both abacavir DISI and flucloxacillin DILI but the reasons for the different phenotype of ADR remains unknown.
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.
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.
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>).
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 the pilot study, the frequency of HLA-B*35:01 was 45.4% in PM-DILI patients compared with 2.7% in the Han Chinese population (odds ratio [OR], 30.4; 95% confidence interval [CI], 11.7-77.8; P = 1.9 × 10<sup>-10</sup> ).
In a multivariate logistic analysis, the proportion of patients carrying <i>HLA-B</i><sup>*</sup><i>57</i> (<i>P</i> = 0.002) and <i>HLA-B</i><sup>*</sup><i>14</i> (<i>P</i> = 0.014) alleles were significantly higher in DILI cases compared with treatment tolerants.