Abstract
ObjectiveIn a previous cohort study (n=96), we found an association between mitochondrial (mt) DNA haplogroup JT and increased survival of severe septic patients, after controlling for age and serum lactic acid levels. The aim of this research was to increase the predictive accuracy and to control for more confounder variables in a larger cohort (n=196) of severe septic patients, to confirm whether mtDNA haplogroup JT influences short and medium-term survival in these patients.MethodsWe conducted a prospective, multicenter, observational study in six Spanish Intensive Care Units. We determined 30-day and 6-month survival and mtDNA haplogroup in this second cohort of 196 patients and in the global cohort (first and second cohorts combined) with 292 severe septic patients. Multiple logistic regression and Cox regression analyses were used to test for the association of mtDNA haplogroups JT with survival at 30-days and 6-months, controlling for age, sex, serum interleukin-6 levels and SOFA score.ResultsLogistic and Cox regression analyses showed no differences in 30-day and 6-month survival between patients with mtDNA haplogroup JT and other haplogroups in the first cohort (n=96). In the second cohort (n=196), these analyses showed a trend to higher 30-day and 6-month survival in those with haplogroup JT. In the global cohort (n=292), logistic and Cox regression analyses showed higher 30-day and 6-month survival for haplogroup JT. There were no significant differences between J and T sub-haplogroups in 30-day and 6-month survival.ConclusionsThe global cohort study (first and second cohorts combined), the largest to date reporting on mtDNA haplogroups in septic patients, confirmed that haplogroup JT patients showed increased 30-day and 6-month survival. This finding may be due to single nucleotide polymorphism defining the whole haplogroup JT and not separately for J or T sub-haplogroups.
Highlights
Severe sepsis is a common, expensive, and frequently fatal condition [1,2]
Multiple logistic regression and Cox regression analyses showed that mitochondrial DNA (mtDNA) haplogroup JT was associated with higher survival at 30-days or 6 months after controlling for age, sex, serum interleukin-6 levels and sepsis-related organ failure assessment (SOFA) score (Table 2)
In the first cohort (n=96) we found no significant differences between patients with the mtDNA haplogroup JT (n=15) and other haplogroups (n=81) in survival at 30 days (86.7% vs 61.7%; p=0.17) and 6 months (73.3% vs 53.1%; p=0.08)
Summary
Severe sepsis is a common, expensive, and frequently fatal condition [1,2]. Genetic factors may influence mortality in septic patients. Sepsis-related polymorphism studies have most commonly focused on genetic variants for specific genes whose protein products are elements of biologic pathways implicated in sepsis. These have included pro- and antiinflammatory cytokines, innate immunity and coagulation/ fibrinolysis pathways [3,4,5]. In 137 and 181 septic patients from a Chinese Han population, mtDNA macrolineage R was found to be a strong independent predictor of sepsis survival at 30 days [7] and six-months [8], respectively. In 148 septic patients from England, haplogroup H was found to be a strong independent predictor of six-month outcome in patients with severe sepsis [6]. In 96 septic patients from Spain, we found that mtDNA haplogroup JT was associated with higher one-month survival, after controlling for age and serum lactic acid levels [9]
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