Genetic Regulation of Protein Biomarkers in Pediatric Acute Respiratory Distress Syndrome
Guy Helman, Rui Feng, Joshua E. Motelow, Nadir YehyaOBJECTIVES:
Acute respiratory distress syndrome (ARDS) is a significant contributor to ICU admissions, morbidity, and mortality. Biomarkers have increasingly been used to dissect heterogeneity and mechanisms underlying pediatric ARDS. We sought to assess the genetic contribution to the levels of protein biomarkers currently used to subphenotype pediatric ARDS patients.
DESIGN, SETTING, AND PARTICIPANTS:
Retrospective, single-center cohort study at a tertiary care PICU of children (< 18 yr) with pediatric ARDS diagnosis.
INTERVENTIONS:
None.
MEASUREMENTS AND MAIN RESULTS:
Genome-wide protein quantitative trait loci (pQTL) analysis was performed on biomarkers measured on day 0 of ARDS, which were previously associated with outcomes from a single-center cohort using linear regression models. We then assessed the genetic association with longitudinal biomarker levels (on days 0, 3, and 7) and with 28-day survival using linear mixed-effects models and Cox proportional hazard models, respectively. From 333 children with ARDS, 267 underwent pQTL analysis against 6 preselected protein biomarkers. Among the patients, 49.4% had ARDS attributed to infectious pneumonia, and 21.7% had ARDS resulting from nonpulmonary sepsis. The hypoinflammatory phenotype was identified in 74.2% of patients, and overall mortality was 14.6%. One single nucleotide polymorphism (SNP) was identified in
CONCLUSIONS:
We identified a gene-associated SNP in