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

doi:10.1016/j.isci.2023.108333

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

iScience. 2023 Oct 28;26(12):108333. doi: 10.1016/j.isci.2023.108333. eCollection 2023 Dec 15.

Authors

Fayten El-Dehaibi¹, Ruben Zamora¹, Josiah Radder², Jinling Yin¹, Ashti M Shah³, Rami A Namas¹, Michelle Situ¹, Yanwu Zhao², William Bain², Alison Morris², Bryan J McVerry², Derek A Barclay¹, Timothy R Billiar¹, Yingze Zhang², Georgios D Kitsios², Yoram Vodovotz^{1

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Affiliations

¹ Department of Surgery, University of Pittsburgh, Pittsburgh, PA 15213, USA.
² Division of Pulmonary, Allergy and Critical Care Medicine, Department of Medicine, University of Pittsburgh, Pittsburgh, PA 15213, USA.
³ Physician Scientist Training Program, University of Pittsburgh, Pittsburgh, PA 15213, USA.
⁴ Center for Inflammation and Regeneration Modeling, McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, PA 15219, USA.
⁵ Center for Systems Immunology, University of Pittsburgh, Pittsburgh, PA 15213, USA.

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.

Keywords: Clinical genetics; Health sciences; Medicine.

Abstract

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