An Aging-Related Single-Nucleotide Polymorphism is Associated With Altered Clinical Outcomes and Distinct Inflammatory Profiles in Aged Blunt Trauma Patients

Shock. 2020 Feb;53(2):146-155. doi: 10.1097/SHK.0000000000001411.


The contribution of individual genetic determinants of aging to the adverse clinical outcomes and altered inflammation mediator networks characteristic of aged trauma patients is unknown. The AA genotype of the aging-related single-nucleotide polymorphism (SNP) rs2075650 in TOMM40 has been associated with longevity, while the AG and GG genotypes are associated with an increased risk of Alzheimer disease. Here, we studied the effect of rs2075650 on clinical outcomes and dynamic biomarker patterns after traumatic injury. Genomic DNA was obtained from blunt trauma patients admitted to the ICU and examined for 551,839 SNPs using an Illumina microarray kit. Plasma was sampled from each patient three times within the first 24 h and daily from day 1 to 7 then assayed for 31 biomarkers using Luminex. Aged patients (65-90 years) were segregated into AA (n = 77) and AG/GG (n = 17) genotypes. Additional comparisons were made with matched groups of young patients (18-30 years), controlling for injury severity score (ISS) and sex ratio, and also segregated into AA (n = 56) and AG/GG (n = 19) genotypes. Aged patients with the AA genotype had a significantly lower requirement for ventilation and fewer days on mechanical ventilation, as well as significantly higher levels of one mediator and lower levels of two mediators. Dynamic Bayesian Network inference revealed IL-23 as a central node in each network regardless of age or genotype, with MIG and IP-10 also as key mediators in the networks of the aged patients. These findings suggest that an aging-related SNP, rs2075650, may influence clinical outcomes and inflammation networks in aged patients following blunt trauma, and thus may serve as a predictive outcome biomarker in the setting of polytrauma.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Aged
  • Aged, 80 and over
  • Aging / genetics
  • Aging / physiology
  • Bayes Theorem
  • Biomarkers / blood
  • Female
  • Genotype
  • Humans
  • Injury Severity Score
  • Male
  • Polymorphism, Single Nucleotide / genetics*
  • Real-Time Polymerase Chain Reaction
  • Respiration, Artificial
  • Retrospective Studies
  • Wounds and Injuries / blood*
  • Wounds and Injuries / genetics*
  • Wounds, Nonpenetrating / genetics*
  • Wounds, Nonpenetrating / immunology*


  • Biomarkers