Gene variants for meningitis susceptibility discovered
10 August 2010
The discovery, by researchers from Imperial College London and the Genome Institute of Singapore, suggests that people who develop these diseases have innate differences in their natural defences that leave their immune system unable to attack meningococcal bacteria successfully.
Meningococcal meningitis and septicaemia most commonly affect babies, children and young people, and can cause critical illness within hours of infection. Although several different bacteria and viruses cause meningitis, the bacteria-borne meningococcal meningitis is one of the most devastating forms - around one in ten cases ends in death. However, most people carry the meningococcal bacteria in their throat intermittently during their lives without ever developing the disease.
In the study, scientists looked at the genomes of 1500 people who developed meningococcal meningitis and over 5000 healthy people from Austria, Holland, Spain and the UK, including data from the Wellcome Trust Case Control Consortium.
Those who developed meningococcal meningitis were found to have distinct markers around the genes for factor H and factor H-related proteins. These regulate a part of the body's immune system called the complement system, which recognises and kills invading bacteria.
Normally, factor H and factor H-related proteins ensure that the complement system does not cause excessive damage to the body's own cells. Previous Trust-funded research has revealed that meningococcal bacteria hijack the body's factor H, using it as a disguise so that the bacteria can evade the body's defences.
"Although most of us have carried the meningitis bacteria at some point, only around one in 40 000 people develop meningococcal meningitis," said Professor Michael Levin from Imperial, who led the study. "Our findings provide the strongest evidence so far that there are genetic factors that lead to people developing meningitis."
The research team will now investigate precisely how the genetic variations affect factor H and factor H-related protein activity.
They hope that their research will boost the development of effective vaccines to combat the group B strain of the bacteria, which causes thousands of deaths each year and for which there is currently no vaccine.
This research was supported by the Meningitis Research Foundation UK, the European Society for Paediatric Infectious Diseases and the Wellcome Trust.
Image: Ultrasonic meningitis test - positive sample. Credit: Dr Mike Sobanski, Wellcome Images
Reference
Davila S et al. Genome-wide association study identifies variants in the CFH region associated with host susceptibility to meningococcal disease. Nat Genet 2010 [Epub ahead of print].
