BioWorld International Correspondent

LONDON - Whether someone survives the multiple organ failure that can follow severe infection - a condition known as sepsis - might depend on whether they have a certain variant of DNA within their mitochondria.

New research showed that people with one variant of mitochondrial DNA who were admitted to an intensive care unit with sepsis had much higher survival rates than those with other variants.

The genetic variant might alter the way in which the mitochondria convert food into energy and might allow the body to reach a higher temperature in order to fight the infection. In the study, the average temperature of people who survived was significantly higher than that of people who died.

Researchers now want to elucidate the mechanism by which those with one genetic variant have a lower risk of dying from sepsis. They hope that will give them clues for new ways to treat sepsis.

Patrick Chinnery, professor of neurogenetics at the University of Newcastle, in Newcastle-upon-Tyne, UK, told BioWorld International: "This finding is very important because 40 percent of people who are admitted to an intensive care unit with sepsis die, despite all treatment. We have now opened up a completely new avenue to investigate and understand the process of how the body deals with sepsis. Hopefully, this means we will one day be able to develop new treatments and reduce the death rate associated with this condition."

It will be possible to identify patients on the intensive care unit who are less likely to survive a severe infection. Clinicians will want to investigate whether providing more aggressive clinical care for that group will improve the outcome, he added.

The research first appeared in the Dec. 17, 2005, issue of The Lancet in a paper titled "Mitochondrial DNA and survival after sepsis: A prospective study." The first author is Simon Baudouin.

Independent studies already had suggested that the mitochondria of people who succumbed to severe infections might not work as they should. But no one knew whether that mitochondrial defect was the cause of the sepsis, or whether the sepsis was the cause of the defect.

Chinnery, Baudouin and colleagues decided to investigate whether there was a link between the type of mitochondrial DNA and the outcome in sepsis.

The team recruited 150 patients with severe sepsis who were admitted sequentially to the intensive care unit at the Royal Victoria Infirmary in Newcastle-upon-Tyne and, with permission, analyzed their mitochondrial DNA.

Looking for single nucleotide polymorphisms, the team divided the patients into the 10 most common groups, or haplotypes, of mitochondrial DNA.

Comparison with a control group showed that there was no difference between the frequency of the different haplotypes in the general population and that in the study population. In other words, a person's mitochondrial DNA haplotype does not dictate his or her risk of developing sepsis and ending up in intensive care.

However, once there, Chinnery and his team showed that those with mitochondrial DNA haplotype H were more than twice as likely to survive to six months than those with other haplotypes.

Chinnery concluded that mitochondria clearly play a role in dealing with the severe insult of infection. "We need to look carefully at the mechanisms involved," he said. "It may be possible to develop treatments for use in intensive care."

The study also showed that the maximum temperature generated by people with haplotype H who were in the intensive care unit was significantly greater than those with other haplotypes. Among those of haplotype H in intensive care, those who survived for six months had a higher maximum temperature than those who did not survive.

The finding raises the hypothesis, Chinnery said, that genetic variants that make the mitochondria less efficient at producing adenosine triphosphate but allow them to generate more heat could give a survival advantage.

"Raising body temperature is a primitive mechanism for fighting infection," he added. "If we could work on stimulating this mechanism for fighting infection, because it is not a specific response to a particular microorganism," then resistance problems would be unlikely.