A common single nucleotide polymorphism is associated with inflammation and critical illness outcomes

Fayten El-Dehaibi, Ruben Zamora, Josiah Radder, Jinling Yin, Ashti M. Shah, Rami A. Namas, Michelle Situ, Yanwu Zhao, William Bain, Alison Morris, Bryan J. McVerry, Derek A. Barclay, Timothy R. Billiar, Yingze Zhang, Georgios D. Kitsios, Yoram Vodovotz*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Acute inflammation is heterogeneous in critical illness and predictive of outcome. We hypothesized that genetic variability in novel, yet common, gene variants contributes to this heterogeneity and could stratify patient outcomes. We searched algorithmically for significant differences in systemic inflammatory mediators associated with any of 551,839 SNPs in one derivation (n = 380 patients with blunt trauma) and two validation (n = 75 trauma and n = 537 non-trauma patients) cohorts. This analysis identified rs10404939 in the LYPD4 gene. Trauma patients homozygous for the A allele (rs10404939AA; 27%) had different trajectories of systemic inflammation along with persistently elevated multiple organ dysfunction (MOD) indices vs. patients homozygous for the G allele (rs10404939GG; 26%). rs10404939AA homozygotes in the trauma validation cohort had elevated MOD indices, and non-trauma patients displayed more complex inflammatory networks and worse 90-day survival compared to rs10404939GG homozygotes. Thus, rs10404939 emerged as a common, broadly prognostic SNP in critical illness.

Original languageEnglish
Article number108333
JournaliScience
Volume26
Issue number12
DOIs
StatePublished - 15 Dec 2023
Externally publishedYes

Keywords

  • Clinical genetics
  • Health sciences
  • Medicine

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