Genetic Regulation of Protein Biomarkers in Pediatric Acute Respiratory Distress Syndrome.

Authors

Guy Helman, Rui Feng, Joshua E Motelow, Nadir Yehya

Published in

Critical care explorations. Volume 8. Issue 8. Pages e1468. Aug 01, 2026. Epub Aug 17, 2026.

Abstract

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.
Retrospective, single-center cohort study at a tertiary care PICU of children (< 18 yr) with pediatric ARDS diagnosis.
None.
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 SFTPD with presumed cis-regulatory effect. Linear mixed-effect modeling confirmed the effect of the SNP on biomarker levels in heterozygous or homozygous carriers on day 0 of ARDS course. Survival analysis demonstrated no significant impact on mortality risk.
We identified a gene-associated SNP in SFTPD that impacts relevant biomarker levels in pediatric ARDS. Further characterization is needed to better understand subphenotypes in pediatric ARDS, including genetic determinants of the biomarker levels used to define them.

PMID:
42610802
Bibliographic data and abstract were imported from PubMed on 18 Aug 2026.

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