Population-specific Risk of Pharmacogenomics-related Inaccurate Drug Dosing of ICU Patients

RationaleIntensive care units (ICU) patients are highly vulnerable to inaccurate drug dosing. Pharmacogenomics (PGx) characterizes the influence of inherited genetic variation on drug metabolism, playing an important role in the consequences of a given drug dose. ObjectivesTo assess the genetic-based risk of inaccurate drug dosing in the ICU. MethodsWe carried out whole genome sequencing (WGS) of 210 Qataris in ICU care at Hamad Medical Corporation (HMC), Doha, Qatar and assessed the WGS for predicted deleterious variants of genes that metabolize 30 drugs commonly prescribed in the ICU. Measurements and Main ResultsAnalysis of 210 Qatari ICU WGS identified 329 variants predicted deleterious associated with 85 genes known to affect metabolism of the 30 ICU drugs. Of the ICU patients that received the 5 most commonly prescribed drugs (warfarin, phenytoin, midazolam, vancomycin, levetiracetam), 93% had deleterious metabolism-related variants. Most (91%) patients carried at least one variant in a gene that that had the potential to affect the metabolism or activity of at least 1 drug that the patient received. Most patients had [≥]14 deleterious variants of genes that affect the metabolism of administered drugs. Comparison of the deleterious variants related to metabolism of ICU drugs with African/African American and European populations revealed significant population specificity in ICU related PGx variants. ConclusionsTogether, these data suggest that population specific, pharmacogenomics based on the individuals genome likely plays a significant role in effective, safe dosing in the ICU setting.