Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Multicenter Study
. 2012 Jan 17;16(1):R10.
doi: 10.1186/cc11150.

Survival and mitochondrial function in septic patients according to mitochondrial DNA haplogroup

Leonardo Lorente  1 , Ruth Iceta, María M Martín, Esther López-Gallardo, Jordi Solé-Violán, José Blanquer, Lorenzo Labarta, César Díaz, Alejandro Jiménez, Julio Montoya, Eduardo Ruiz-Pesini
Affiliations
Multicenter Study

Survival and mitochondrial function in septic patients according to mitochondrial DNA haplogroup

Leonardo Lorente et al. Crit Care. .

Abstract

Introduction: We recently found that platelet cytochrome c oxidase (COX) activities and quantities in 6-month-survival septic patients are significantly higher than those of patients who died before 6 months. Other studies suggested that the mitochondrial DNA (mtDNA) genotype could play a major role in sepsis survival. Given that COX catalytic subunits are encoded by mtDNA, the objective of the present study was to explore whether mtDNA population genetic variation could affect COX activity and quantity and favors sepsis survival.

Methods: A prospective, multicenter, observational study was carried out in six Spanish ICUs. We included 96 patients with severe sepsis. We determined the mtDNA haplogroup, the COX specific activity/citrate synthase specific activity (COXa/CSa) ratio and the COX quantity/citrate synthase specific activity (COXq/CSa) ratio in circulating platelets at the time of diagnosis, day 4 and day 8. We used survival at 1 and 6 months as endpoints.

Results: Patients with the JT mtDNA haplogroup (n=15) showed higher COXq/CSa ratio at day 4 (P=0.04) and day 8 (P=0.02) than those with other haplogroups (n=81). Logistic regression analysis showed that the JT mtDNA haplogroup (odds ratio=0.18; 95% confidence interval=0.04 to 0.94; P=0.04) and COXq/CSa ratio (odds ratio=0.53; 95% confidence interval=0.30 to 0.93; P=0.03) were associated with 1-month survival after controlling for age and lactic acid levels.

Conclusions: The novel findings of our study are that 1-month surviving septic patients showed higher COXq/CSa ratio than nonsurviving individuals, that patients from the JT mtDNA haplogroup showed a higher COXq/CSa ratio and that JT patients had a higher 1-month survival than patients from other mtDNA haplogroups.

PubMed Disclaimer

Figures

Figure 1
Figure 1
Human mitochondrial DNA haplogroups.
Figure 2
Figure 2
Association of survival with the JT mitochondrial DNA haplogroup. Cumulative proportion of surviving patients at 6 months according to the JT mitochondrial DNA (mtDNA) haplogroup versus non-JT mtDNA haplogroup.
See this image and copyright information in PMC

References

    1. Vincent JL, Sakr Y, Sprung CL, Ranieri VM, Reinhart K, Gerlach H, Moreno R, Carlet J, Le Gall JR, Payen D. Sepsis in European intensive care units: results of the SOAP study. Crit Care Med. 2006;34:344–353. doi: 10.1097/01.CCM.0000194725.48928.3A. - DOI - PubMed
    1. Angus DC, Linde-Zwirble WT, Lidicker J, Clermont G, Carcillo J, Pinsky MR. Epidemiology of severe sepsis in the United States: analysis of incidence, outcome, and associated costs of care. Crit Care Med. 2001;29:1303–1010. doi: 10.1097/00003246-200107000-00002. - DOI - PubMed
    1. Fink M. Cytopathic hypoxia in sepsis. Acta Anaesthesiol Scand Suppl. 1997;110:87–95. - PubMed
    1. Lorente L, Martín MM, López-Gallardo E, Iceta R, Solé-Violán J, Blanquer J, Labarta L, Díaz C, Jiménez A, Lafuente N, Hernández M, Méndez F, Medina N, Ferrer-Agüero JM, Ferreres J, LLimiñana MC, Mora ML, Lubillo S, Sánchez-Palacios M, Montoya J, Ruiz-Pesini E. Platelet cytochrome c oxidase activity and quantity in septic patients. Crit Care Med. 2011;39:1289–1294. doi: 10.1097/CCM.0b013e31820ee20c. - DOI - PubMed
    1. Fernández-Vizarra E, Tiranti V, Zeviani M. Assembly of the oxidative phosphorylation system in humans: what we have learned by studying its defects. Biochim Biophys Acta. 2009;1793:200–211. doi: 10.1016/j.bbamcr.2008.05.028. - DOI - PubMed

Publication types

Substances