Identification of the Epigenetic Response to Trauma
Condition: Trauma; Injuries
MeSH terms: Wounds and Injuries
Study type: Observational

Summary: 
      The objective of this study is to investigate potential early alterations in the DNA
      methylation profile after severe trauma and to investigate if the early marks persist.
    

Detailed description: 
      Background: Severe trauma is an extreme physical exposure, which may have significant
      consequences for the patient. In addition to anatomical injury and hemodynamic compromise,
      severe trauma causes an immense and rapid systemic immune reaction. At the genomic level,
      trauma has been found to significantly increase gene expression in circulating leukocytes,
      and preliminary data is also emerging that trauma may even cause epigenetic (DNA methylation)
      alterations.

      Epigenetics, including DNA methylation, have been suggested as a mediator of genetic risk and
      to play a significant role in subsequent non-traumatic disease. Within the field of trauma
      DNA methylation has only been sparsely studied, but a few studies of traumatized animals have
      suggested that DNA methylation alterations may occur in relation to trauma. Even though DNA
      methylation is highly dynamic, some marks have been found to be stable over time, and thus
      may have long-term consequences.

      An increasing understanding of the role of epigenetics in disease development and response
      may pave the way for new treatment targets and modalities for multiple diseases including
      trauma.

      Research question: Does trauma induce immediate (<4 hours) and persistent (30 days
      post-trauma) changes in the epigenome of peripheral blood cells, and do epigenetic changes
      correlate with patient recovery?

      Objectives: To identify potential early alterations in the DNA methylation profile after
      severe trauma AND to investigate if the early marks persist.

      Study design: A prospective, observational, cohort study of trauma patients admitted to RH's
      trauma center. The trauma cohort will be compared to a cohort of patients admitted for
      elective orthopedic surgery in terms of DNA methylation profile in blood cells
      pre-trauma/surgery, immediately post-trauma/surgery, and 30-45 days post-trauma/surgery.

      DNA methylation profiles will be assessed by array technique using Illumina's MethylationEPIC
      Bead-Chip.

      Primary outcome: Immediate (<4 hours) post-trauma DNA methylation profile in blood cells.

      Secondary outcomes: Pre-trauma/surgery DNA methylation profile, change in DNA methylation
      from pre-trauma/surgery to immediately and 30 days post-trauma/surgery, occurrence of organ
      dysfunction, sepsis, septic shock, 30-day mortality, ICU admission > 24 hours, ICU length of
      stay (LOS), hospital LOS.
    

Intervention name(s): Blood samples for DNA methylation analysis
Intervention type(s): Diagnostic Test
Intervention description(s): DNA from blood samples will be isolated and analyzed for genome-wide DNA methylation patterns using the Infinium HumanMethylationEPIC BeadChip (Illumina, San Diego, CA, USA).
Observational model: Cohort
Time perspective: Prospective
Sampling method: Probability Sample
Study population: 
        The study population consists of all trauma patients admitted to RH's trauma center
        generating a trauma team activation.

        The control group will consist of patients admitted to RH's orthopedic department for
        elective surgery.
      
Biospecimen description: 
      Blood samples are obtained from patients to investigate DNA methylation profiles
    
Keywords: Epigenetics; DNA methylation; Trauma