Multiomic molecular patterns of lipid dysregulation in a subphenotype of sepsis with higher shock incidence and mortality
Authors' conclusion
We identified a genetic lipid dysregulation signature characterized by seven lipid metabolism genes. Five genes in HYPO sepsis patients most strongly correlated with low CE, LPC, and SMs that mediate cholesterol storage and innate immunity.
Study context
- Population
- Adults with sepsis, leukocytes collected within 24 h of sepsis
- Participants
- 288 adults · 4 sepsis studies
- Exposure
- Hypolipoprotein (HYPO) vs normolipoprotein (NORMO) lipid dysregulation subphenotypes
- Outcome
- Gene expression and lipidomic patterns
Methodological detailssecondary analysis of four adult sepsis cohorts, external validation in two datasets, leukocyte RNA sequencing, shotgun plasma lipidomics
- Secondary analysis of four adult sepsis cohorts
- External validation in two datasets
- Leukocyte RNA sequencing
- Shotgun plasma lipidomics
Main finding
As reported in the abstract
- Lower cholesterol esters (CE) in HYPO
- adjusted p = < 0.001
- Lower lysophosphatidylcholines (LPC) in HYPO
- adjusted p = 0.001
- Lower sphingomyelins (SM) in HYPO
- adjusted p = < 0.001
- In HYPO, DHCR7 expression strongly correlated with reductions in CE, LPC and SM
- p < 0.01
- PCSK9, MSMO1, DHCR7, PLTP and LDLR upregulation correlated with low LPC
- p < 0.05
- DHCR7, ALOX5 and LDLR correlated with reductions in SM
- p < 0.05
Observational data: associations, not effects.
Further findings
Subphenotype distribution
Vasopressor use
P = < 0.001
Mortality · 28 days
P = 0.004
Median
| Outcome | HYPO | NORMO | P value |
|---|---|---|---|
| SOFA score | 9 | 5 | P = < 0.001 |
External validation (two datasets)
- Mortality and phenotype comparisons corroborated six of the seven upregulated lipid genes (PCSK9, DHCR7, ALOX5, PLTP, LDLR, MSMO1)
- N = 824 combined patients
Original publication
Multiomic molecular patterns of lipid dysregulation in a subphenotype of sepsis with higher shock incidence and mortality. Crit Care. Published 24 December 2024. doi:10.
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