Abstract
Trauma is a leading cause of morbidity and mortality. It is unclear why some trauma victims follow a complicated clinical course and die, while others, with apparently similar injury characteristics, do not. Interpatient genomic differences, in the form of single nucleotide polymorphisms (SNPs), have been associated previously with adverse outcomes after trauma. Recently, we identified seven novel SNPs associated with mortality following trauma. The aim of the present study was to determine if one or more of these SNPs was also associated with worse clinical outcomes and altered inflammatory trajectories in trauma survivors. Accordingly, of 413 trauma survivors, DNA samples, full blood samples, and clinical data were collected at multiple time points in the first 24 h and then daily over 7 days following hospital admission. Subsequently, single-SNP groups were created and outcomes, such as hospital length of stay (LOS), ICU LOS, and requirement for mechanical ventilation, were compared. Across a broad range of Injury Severity Scores (ISS), patients carrying the rs2065418 TT SNP in the metallophosphoesterase domain-containing 2 (MPPED2) gene exhibited higher Marshall MODScores vs. the control group of rs2065418 TG/GG patients. In patients with high-severity trauma (ISS ≥ 25, n = 94), those carrying the rs2065418 TT SNP in MPPED2 exhibited higher Marshall MODScores, longer hospital LOS (21.8 ± 2 days), a greater requirement for mechanical ventilation (9.2 ± 1.4 days on ventilator, DOV), and higher creatinine plasma levels over 7 days vs. the control group of rs2065418 TG/GG high-severity trauma patients (LOS: 15.9 ± 1.2 days, p = 0.03; DOV: 5.7 ± 1 days, p = 0.04; plasma creatinine; p < 0.0001 MODScore: p = 0.0003). Furthermore, rs2065418 TT patients with ISS ≥ 25 had significantly different plasma levels of nine circulating inflammatory mediators and elevated dynamic network complexity. These studies suggest that the rs2065418 TT genotype in the MPPED2 gene is associated with altered systemic inflammation, increased organ dysfunction, and greater hospital resource utilization. A screening for this specific SNP at admission might stratify severely injured patients regarding their lung and kidney function and clinical complications.
Highlights
Traumatic injury is the third leading cause of death in the United States, with estimated costs exceeding $130 billion annually (Palmer, 2007; Soreide, 2009; Dwyer-Lindgren et al, 2016)
The present study investigated a single nucleotide polymorphisms (SNPs) in the metallophosphoesterase domaincontaining 2 (MPPED2) gene associated with altered inflammation and adverse clinical outcomes in severe blunt trauma
Over the past 30 years, intense research on the immunological response of trauma has led to a growing list of immune cell populations and inflammatory mediators linked with adverse outcomes (Lord et al, 2014; Namas et al, 2015)
Summary
Traumatic injury is the third leading cause of death in the United States, with estimated costs exceeding $130 billion annually (Palmer, 2007; Soreide, 2009; Dwyer-Lindgren et al, 2016). Major trauma resulting in an ISS ≥ 16 is considered “moderate,” while an ISS ≥ 25 is considered “severe” trauma (Palmer, 2007; Almahmoud et al, 2015). ISS is positively correlated with altered systemic inflammation, increasing rates of complications such as multiple organ dysfunction (MOD, which can be evaluated using the Marshall MODScore among others), prolonged hospitalization, and increased mortality (Pettit et al, 2014; Almahmoud et al, 2015). SNPs are defined as single variants of one base in the genome and are the most common type of inter-individual genetic variability (Syvanen, 2001)
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