title: Survival and mitochondrial function in septic patients according to mitochondrial DNA haplogroup.
abstract: BACKGROUND
  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.
authors.affiliation: Intensive Care Unit, Hospital Universitario de Canarias, La Laguna 38320, Santa Cruz de Tenerife, Spain. lorentemartin@msn.com
authors.forename: Leonardo
authors.initials: L
authors.lastname: Lorente
authors.forename: Ruth
authors.initials: R
authors.lastname: Iceta
authors.forename: María M
authors.initials: MM
authors.lastname: Martín
authors.forename: Esther
authors.initials: E
authors.lastname: López-Gallardo
authors.forename: Jordi
authors.initials: J
authors.lastname: Solé-Violán
authors.forename: José
authors.initials: J
authors.lastname: Blanquer
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Labarta
authors.forename: César
authors.initials: C
authors.lastname: Díaz
authors.forename: Alejandro
authors.initials: A
authors.lastname: Jiménez
authors.forename: Julio
authors.initials: J
authors.lastname: Montoya
authors.forename: Eduardo
authors.initials: E
authors.lastname: Ruiz-Pesini
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D004272:DNA, Mitochondrial / Q000235:genetics*; D005260:Female; D006239:Haplotypes / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D008928:Mitochondria / Q000502:physiology*; D011446:Prospective Studies; D018805:Sepsis / Q000235:genetics* / Q000401:mortality* / Q000503:physiopathology; D015996:Survival Rate / Q000639:trends
chemical_list: D004272:DNA, Mitochondrial