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PPARγ Variant rs10865710 and Mortality in Pediatric Septic Shock Stratified by Corticosteroid Exposure

Valentina Bonnefil1, Stephen Standage1,2, Andrew J Lautz1,2

  • 1Division of Critical Care Medicine, Cincinnati Children's Hospital Medical Center, Cincinnati, OH.

Critical Care Explorations
|May 25, 2026
PubMed

Insights

Genetic variation in peroxisome proliferator-activated receptor gamma (PPARγ) influences mortality in pediatric septic shock, particularly in patients receiving corticosteroids. The PPARγ variant rs10865710 is linked to increased mortality risk.

Area of Science:

  • Genetics and Molecular Biology
  • Pediatric Critical Care Medicine
  • Pharmacogenomics

Background:

  • Pediatric septic shock is a life-threatening condition with significant mortality.
  • Genetic factors may influence patient outcomes in septic shock.
  • Peroxisome proliferator-activated receptor gamma (PPARγ) plays a role in inflammatory and metabolic processes relevant to sepsis.

Purpose of the Study:

  • To investigate the association between genetic variations in PPARγ and mortality in children with septic shock.
  • To examine if corticosteroid exposure modifies the relationship between PPARγ genetic variants and septic shock mortality.

Main Methods:

  • A multicenter prospective observational study involving 381 children (1 week to 10 years) with septic shock.
  • Genotyping of two PPARγ single nucleotide variants (SNVs): rs10865710 and rs1801282.
  • Statistical analysis using multivariable logistic regression and Cox proportional hazards models, stratified by corticosteroid exposure.

Main Results:

  • Carriage of the rs10865710 mutant allele was significantly associated with higher 28-day mortality (10.2% vs. 3.5%, p=0.009).
  • The association between rs10865710 and mortality was most pronounced in patients treated with corticosteroids (aOR=5.85, p=0.015; aHR=5.33, p=0.013).
  • No significant association was found for rs1801282 or genotype effects on PPARγ expression, though a trend towards lower glucocorticoid receptor (NR3C1) expression was observed.

Conclusions:

  • The intronic PPARγ variant rs10865710 is linked to increased mortality in pediatric septic shock, especially in corticosteroid-treated patients.
  • Exploratory findings suggest potential alterations in glucocorticoid receptor signaling.
  • Further research is needed to validate these findings and elucidate the underlying mechanisms.
Abstract

Keywords:
corticosteroidsgenetic variantsmetabolismpediatric septic shockperoxisome proliferator-activated receptor

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