Association of mitochondrial allele 4216c with increased risk for sepsis-related organ dysfunction and shock after burn injury

Ryan M. Huebinger, Ruben Gomez, Daphne McGee, Ling Yu Chang, Jessica E. Bender, Terence OKeeffe, Agnes M. Burris, Susan M. Friese, Gary F. Purdue, John L. Hunt, Brett D. Arnoldo, Jureta W. Horton, Robert C. Barber

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

Impaired mitochondrial activity has been linked to increased risk for clinical complications after injury. Furthermore, variant mitochondrial alleles have been identified and are thought to result in decreased mitochondrial activity. These include a nonsynonymous mitochondrial polymorphism (T4216C) in the nicotinamide adenine dinucleotide dehydrogenase 1 gene (ND1), encoding a key member of complex I within the electron transport chain, which is found almost exclusively among Caucasians. We hypothesized that burn patients carrying ND1 4216C are less able to generate the cellular energy necessary for an effective immune response and are at increased risk for infectious complications. The association between 4216C and outcome after burn injury was evaluated in a cohort of 175 Caucasian patients admitted to the Parkland Hospital with burns covering greater than or equal to 15% of their total body surface area or greater than or equal to 5% full-thickness burns under an institutional review board-approved protocol. To remove confounding unrelated to burn injury, individuals were excluded if they presented with significant non-burn-related trauma (Injury Severity Score ≥16), traumatic or anoxic brain injury, spinal cord injury, were HIV/AIDS positive, had active malignancy, or survived less than 48 h postadmission. Within this cohort of patients, carriage of the 4216C allele was significantly associated by unadjusted analysis with increased risk for sepsis-related organ dysfunction or septic shock (P = 0.011). After adjustment for full-thickness burn size, inhalation injury, age, and sex, carriage of the 4216C allele was associated with complicated sepsis (adjusted odds ratio = 3.7; 95% confidence interval, 1.5-9.1; P = 0.005), relative to carriers of the T allele.

Original languageEnglish (US)
Pages (from-to)19-23
Number of pages5
JournalShock
Volume33
Issue number1
DOIs
StatePublished - Jan 1 2010
Externally publishedYes

Fingerprint

Shock
Sepsis
Alleles
Wounds and Injuries
Burns
Inhalation Burns
Electron Transport Complex I
Injury Severity Score
Research Ethics Committees
Body Surface Area
Septic Shock
Spinal Cord Injuries
NAD
Brain Injuries
Oxidoreductases
Acquired Immunodeficiency Syndrome
Odds Ratio
HIV
Confidence Intervals
Genes

Keywords

  • Complex
  • Genetic association
  • Mitochondrial DNA polymorphism
  • Mitochondrial electron transport chain

ASJC Scopus subject areas

  • Emergency Medicine
  • Critical Care and Intensive Care Medicine

Cite this

Association of mitochondrial allele 4216c with increased risk for sepsis-related organ dysfunction and shock after burn injury. / Huebinger, Ryan M.; Gomez, Ruben; McGee, Daphne; Chang, Ling Yu; Bender, Jessica E.; OKeeffe, Terence; Burris, Agnes M.; Friese, Susan M.; Purdue, Gary F.; Hunt, John L.; Arnoldo, Brett D.; Horton, Jureta W.; Barber, Robert C.

In: Shock, Vol. 33, No. 1, 01.01.2010, p. 19-23.

Research output: Contribution to journalArticle

Huebinger, RM, Gomez, R, McGee, D, Chang, LY, Bender, JE, OKeeffe, T, Burris, AM, Friese, SM, Purdue, GF, Hunt, JL, Arnoldo, BD, Horton, JW & Barber, RC 2010, 'Association of mitochondrial allele 4216c with increased risk for sepsis-related organ dysfunction and shock after burn injury', Shock, vol. 33, no. 1, pp. 19-23. https://doi.org/10.1097/SHK.0b013e3181a99508
Huebinger, Ryan M. ; Gomez, Ruben ; McGee, Daphne ; Chang, Ling Yu ; Bender, Jessica E. ; OKeeffe, Terence ; Burris, Agnes M. ; Friese, Susan M. ; Purdue, Gary F. ; Hunt, John L. ; Arnoldo, Brett D. ; Horton, Jureta W. ; Barber, Robert C. / Association of mitochondrial allele 4216c with increased risk for sepsis-related organ dysfunction and shock after burn injury. In: Shock. 2010 ; Vol. 33, No. 1. pp. 19-23.
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abstract = "Impaired mitochondrial activity has been linked to increased risk for clinical complications after injury. Furthermore, variant mitochondrial alleles have been identified and are thought to result in decreased mitochondrial activity. These include a nonsynonymous mitochondrial polymorphism (T4216C) in the nicotinamide adenine dinucleotide dehydrogenase 1 gene (ND1), encoding a key member of complex I within the electron transport chain, which is found almost exclusively among Caucasians. We hypothesized that burn patients carrying ND1 4216C are less able to generate the cellular energy necessary for an effective immune response and are at increased risk for infectious complications. The association between 4216C and outcome after burn injury was evaluated in a cohort of 175 Caucasian patients admitted to the Parkland Hospital with burns covering greater than or equal to 15{\%} of their total body surface area or greater than or equal to 5{\%} full-thickness burns under an institutional review board-approved protocol. To remove confounding unrelated to burn injury, individuals were excluded if they presented with significant non-burn-related trauma (Injury Severity Score ≥16), traumatic or anoxic brain injury, spinal cord injury, were HIV/AIDS positive, had active malignancy, or survived less than 48 h postadmission. Within this cohort of patients, carriage of the 4216C allele was significantly associated by unadjusted analysis with increased risk for sepsis-related organ dysfunction or septic shock (P = 0.011). After adjustment for full-thickness burn size, inhalation injury, age, and sex, carriage of the 4216C allele was associated with complicated sepsis (adjusted odds ratio = 3.7; 95{\%} confidence interval, 1.5-9.1; P = 0.005), relative to carriers of the T allele.",
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