December 19, 2005

mtDNA haplogroup H and sepsis survival

mtDNA haplogroup H is very common in Caucasoids, reaching frequencies of ~50%. This certainly suggested that it may confer some advantage. It would be interesting to do a study on its frequency in several archeo-DNA samples that are now available compared to that in modern populations.

A new study in the Lancet provides the first evidence of a survival advantage for mtDNA haplogroup H. From the BBC news story:
It has long been thought that there may be a connection between the workings of the mitochondria and how the body reacts to fight infections, such as MRSA and pneumonia.

Researchers identified 10 major variants of mtDNA.

Patients from each variant group were monitored and researchers found people with a particular variant - called haplogroup H - were more than twice as likely as those from any of the other groups to survive for six months.

There was no evidence to suggest that people from haplogroup H were any less likely to contract a severe infection in the first instance.


Haplogroup H is the most recent genetic variation to evolve, but is also the most common - 40% of people have it.
The Lancet 2005; 366:2118-2121

Mitochondrial DNA and survival after sepsis: a prospective study

Simon V Baudouin et al.


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.

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.

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.

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.

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