A Genome-Wide Association Study of Serum Metabolite Profiles in Septic Shock Patients.
Crit Care Explor
; 6(1): e1030, 2024 Jan.
Article
en En
| MEDLINE
| ID: mdl-38239409
ABSTRACT
OBJECTIVES:
We sought to assess whether genetic associations with metabolite concentrations in septic shock patients could be used to identify pathways of potential importance for understanding sepsis pathophysiology.DESIGN:
Retrospective multicenter cohort studies of septic shock patients.SETTING:
All participants who were admitted to 27 participating hospital sites in three countries (Australia, New Zealand, and the United Kingdom) were eligible for inclusion. PATIENTS Adult, critically ill, mechanically ventilated patients with septic shock (n = 230) who were a subset of the Adjunctive Corticosteroid Treatment in Critically Ill Patients with Septic Shock trial (ClinicalTrials.gov number NCT01448109).INTERVENTIONS:
None. MEASUREMENTS AND MAINRESULTS:
A genome-wide association study was conducted for a range of serum metabolite levels for participants. Genome-wide significant associations (p ≤ 5 × 10-8) were found for the two major ketone bodies (3-hydroxybutyrate [rs2456680] and acetoacetate [rs2213037] and creatinine (rs6851961). One of these single-nucleotide polymorphisms (SNPs) (rs2213037) was located in the alcohol dehydrogenase cluster of genes, which code for enzymes related to the metabolism of acetoacetate and, therefore, presents a plausible association for this metabolite. None of the three SNPs showed strong associations with risk of sepsis, 28- or 90-day mortality, or Acute Physiology and Chronic Health Evaluation score (a measure of sepsis severity).CONCLUSIONS:
We suggest that the genetic associations with metabolites may reflect a starvation response rather than processes involved in sepsis pathophysiology. However, our results require further investigation and replication in both healthy and diseased cohorts including those of different ancestry.
Texto completo:
1
Base de datos:
MEDLINE
Tipo de estudio:
Clinical_trials
/
Observational_studies
/
Prognostic_studies
/
Risk_factors_studies
Idioma:
En
Revista:
Crit Care Explor
Año:
2024
Tipo del documento:
Article
País de afiliación:
Australia