Genomics and pharmacogenomics of sepsis: so close and yet so far

Abstract

Sapru et al. show in this issue of Critical Care that variants of thrombomodulin and the endothelial protein C receptor, but not protein C, are associated with mortality and organ dysfunction (ventilation-free and organ failure-free days) in ARDS. Hundreds of gene variants have been found prognostic in sepsis. However, none of these prognostic genomic biomarkers are used clinically. Predictive biomarker discovery (pharmacogenomics) usually follows a candidate gene approach, utilizing knowledge of drug pathways. Pharmacogenomics could be applied to enhance efficacy and safety of drugs used for treatment of sepsis (e.g., norepinephrine, epinephrine, vasopressin, and corticosteroids). Pharmacogenomics can enhance drug development in sepsis, which is very important because there is no approved drug for sepsis. Pharmacogenomics biomarkers must pass three milestones: scientific, regulatory, and commercial. Huge challenges remain but great opportunities for pharmacogenomics of sepsis are on the horizon.