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| Mitochondrial Genetic Polymorphisms, Energy Production and Increased Mortality: A Study of 720 Consecutive Trauma Patients | Jeffery A Canter*1, Judith M Jenkins*1, Patrick R Norris*1, Jason H Moore*2, John A Morris, Jr.1
1Vanderbilt University Medical Center, Nashville, TN;2Dartmouth-Hitchcock Medical Center, Lebanon, NH
| OBJECTIVE(S): The mitochondrial genome (distinct from the nuclear genome) plays a central role in cellular energy production and apoptosis. Trauma represents a “stress phenotype” characterized by high-energy demand, inflammation, free radical production and high mortality. We hypothesized:
Patients with mitochondrial (mtDNA) polymorphisms have altered metabolic response to injury, increasing mortality.
METHODS: 720 consecutive patients admitted to the trauma ICU, with IRB approval, had blood sampled within 24 hours of admission, and were stratified by race (mtDNA differs). Covariates (gender, age, admission lactate and injury severity score) were linked. Caucasians (N=528) were sampled for specific Complex I mtDNA polymorphisms T4216C, A4917G, and A10398G using a flurogenic 5' nuclease allelic discrimination Taqman assay and analyzed using the ABI 7900HT Sequence Detection System (v2.1).
RESULTS: 69 patients died (mortality for 4216T=14.4%, 4216C=8.2%). Multivariate logistic regression analysis revealed that the mtDNA 4216T allele was a significant independent predictor of in-hospital mortality (OR=2.43, 95% CI 1.12 -5.25, p=0.02) after adjustment for age, male gender, injury severity score, lactate and the mtDNA A10398G polymorphism (Table).
CONCLUSIONS: 1. Mitochondrial polymorphisms, specifically the 4216T allele, in Complex I of the electron transport chain may increase the risk of death in critically injured patients after adjusting for covariates.
2. Variation in the mitochondrial genome may explain differences in “stress phenotype” outcomes, and has implications for managing critically ill patients.
| OR | 95% CI | P-value | | 4216T | 2.43 | 1.12 - 5.25 | 0.02 | | 10398A | 0.62 | 0.32 - 1.17 | 0.14 | | Age (years) | 1.04 | 1.01 - 1.05 | <0.01 | | Male Gender | 2.02 | 1.05 - 3.87 | 0.03 | | ISS | 1.06 | 1.04 - 1.09 | <0.01 | | OR=Odds Ratio, CI=Confidence Interval, ISS=Injury Severity Score |
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