Specific Polymorphic Variation in the Mitochondrial Genome and Increased In-hospital Mortality After Severe Trauma.
From: Center for Human Genetics Research, Department of Molecular Physiology and Biophysics, Vanderbilt University Medical Center, Nashville, Tennessee 37212, USA. jeff.canter@vanderbilt.edu
Annals of surgery
- Publish Date: Sep 2007
- ISSN: 0003-4932
- Volume: 246
- Issue: 3
- Pages: 406-11; discussion 411-4
- Medium: Print
- Language: English
- Citation (JAMA): Canter Jeffrey A, Norris Patrick R, Moore Jason H, et al. Specific Polymorphic Variation in the Mitochondrial Genome and Increased In-hospital Mortality After Severe Trauma.. Ann. Surg. Sep 2007;246:406-11; discussion 411-4
Abstract
OBJECTIVE: To determine whether specific genetic variations in the mtDNA that impact energy production and free-radical generation are potential new risk factors for in-hospital mortality after severe trauma. SUMMARY BACKGROUND DATA: Each of the 3 mitochondrial DNA polymorphisms selected for this study (at positions 4216, 10398, 4917) alter the amino acid sequence of different key subunits of Complex I in the electron transport chain. They have been previously implicated in phenotypes involving tissues with high-energy demand, such as the brain and retina. METHODS: Seven hundred forty-five consecutive patients admitted to the trauma intensive care unit at Vanderbilt University Medical Center between April 11, 2005, and February 27, 2006, were potentially eligible for this study. Under an Institutional Review Board-approved protocol (which excluded patients <18 years of age and prisoners), 666 patients had DNA extracted from a blood sample. Detailed demographic and clinical covariates were also obtained (including age, gender, ethnicity, lactate measurements, and injury severity score). A flurogenic 5’ nuclease allelic discrimination Taqman assay and the ABI 7900HT Sequence Detection System (v2.1) was used to genotype the T4216C, A10398G, and A4917G polymorphisms. The primary outcome was in-hospital mortality. RESULTS: Multivariate logistic regression analysis revealed that the 4216T allele was a significant independent predictor of in-hospital mortality (OR = 2.63, 95% CI 1.14-6.07, P = 0.02) after adjustment for age, gender, injury severity score, highest lactate level, mechanism of injury, and the 10398 polymorphism. CONCLUSIONS: Variation in the mtDNA, specifically the 4216T allele, appears to increase the risk of in-hospital mortality after severe injury.
Mesh Headings (Keywords): Adult, Alleles, Chi-Square Distribution, DNA, Mitochondrial, Female, Genome, Human, Genotype, Hospital Mortality, Humans, Injury Severity Score, Lactates, Logistic Models, Male, Middle Aged, Phenotype, Polymorphism, Genetic, Prospective Studies, Risk Factors, Statistics, Nonparametric, Wounds and Injuries
Check for Full Text / PubMed Unique Identifier (PMID): 17717444
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