Mitochondrial DNA and survival after sepsis: a prospective study.

TitleMitochondrial DNA and survival after sepsis: a prospective study.
Publication TypeJournal Article
Year of Publication2005
AuthorsBaudouin, SV, Saunders, D, Tiangyou, W, Elson, JL, Poynter, J, Pyle, A, Keers, S, Turnbull, DM, Howell, N, Chinnery, PF
JournalLancet
Volume366
Issue9503
Pagination2118-21
Date Published2005 Dec 17
ISSN1474-547X
KeywordsAged, APACHE, Case-Control Studies, DNA, Mitochondrial, Female, Haplotypes, Humans, Intensive Care Units, Logistic Models, Male, Middle Aged, Prospective Studies, Sepsis
Abstract

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.

FINDINGS: 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.

INTERPRETATION: 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.

DOI10.1016/S0140-6736(05)67890-7
Alternate JournalLancet
Citation Key10.1016/S0140-6736(05)67890-7
PubMed ID16360789
Grant List / / Wellcome Trust / United Kingdom