Mitochondrial DNA and survival after sepsis: a prospective study.
BACKGROUND
Human genome evolution has been shaped by infectious disease. Although most genetic studies have focused on the immune system, recovery after sepsis is directly related to physiological reserve that is critically dependent on mitochondrial function. We investigated whether haplogroup H, the most common type of mitochondrial DNA (mtDNA) in Europe, contributes to the subtle genetic variation in survival after sepsis.


METHODS
In a prospective study, we included 150 individuals who were sequentially admitted to the intensive care unit in a hospital in Newcastle upon Tyne, UK. After clinical data were obtained, patients underwent mtDNA haplotyping by analysis with PCR and restriction fragment length polymorphism. As endpoints, we used death during the 6-month period or survival at 6 months.


RESULTS
Follow-up was complete for all study participants, although the haplotype of two patients could not be reliably determined. On admission to the intensive care unit, the frequency of mtDNA haplogroup H in study patients did not differ between study patients admitted with severe sepsis and 542 age-matched controls from the northeast of England. MtDNA haplogroup H was a strong independent predictor of outcome during severe sepsis, conferring a 2.12-fold (95% CI 1.02-4.43) increased chance of survival at 180 days compared with individuals without the haplogroup H.


CONCLUSIONS
Although haplogroup H is the most recent addition to the group of European mtDNA, paradoxically it is also the most common. Increased survival after sepsis provides one explanation for this observation. MtDNA haplotyping offers a new means of risk stratification of patients with severe infections, which suggests new avenues for therapeutic intervention.
Baudouin
Simon V
SV
University Department of Surgical & Reproductive Sciences, University of Newcastle upon Tyne, Newcastle upon Tyne, UK.
Saunders
David
D
Tiangyou
Watcharee
W
Elson
Joanna L
JL
Poynter
Jayne
J
Pyle
Angela
A
Keers
Sharon
S
Turnbull
Douglass M
DM
Howell
Neil
N
Chinnery
Patrick F
PF
D018806:APACHE; D000368:Aged; D016022:Case-Control Studies; D004272:DNA, Mitochondrial / Q000235:genetics*; D005260:Female; D006239:Haplotypes / Q000235:genetics*; D006801:Humans; D007362:Intensive Care Units; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D018805:Sepsis / Q000145:classification / Q000276:immunology / Q000401:mortality*
D004272:DNA, Mitochondrial