Survival and mitochondrial function in septic patients according to mitochondrial DNA haplogroup View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2012-01-17

AUTHORS

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

ABSTRACT

IntroductionWe 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.MethodsA 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.ResultsPatients 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.ConclusionsThe 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. More... »

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http://scigraph.springernature.com/pub.10.1186/cc11150

DOI

http://dx.doi.org/10.1186/cc11150

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https://app.dimensions.ai/details/publication/pub.1013273807

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/22251664


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37 ResultsPatients
38 Spanish ICUs
39 acid levels
40 activity
41 activity ratio
42 age
43 analysis
44 c oxidase activity
45 catalytic subunit
46 cytochrome c oxidase activity
47 day 4
48 day 8
49 diagnosis
50 endpoint
51 findings
52 function
53 genetic variation
54 genotypes
55 haplogroups
56 individuals
57 lactic acid levels
58 levels
59 logistic regression analysis
60 major role
61 mitochondrial DNA genotypes
62 mitochondrial DNA haplogroups
63 mitochondrial function
64 months
65 mtDNA
66 mtDNA haplogroups
67 multicenter
68 novel findings
69 objective
70 observational study
71 oxidase activity
72 patients
73 platelet cytochrome c oxidase activity
74 platelets
75 population genetic variation
76 present study
77 quantity
78 ratio
79 regression analysis
80 role
81 sepsis
82 sepsis survival
83 septic patients
84 severe sepsis
85 specific activity ratio
86 study
87 subunits
88 survival
89 time
90 time of diagnosis
91 variation
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