8 August 2010 Last updated at 17:05 GMT
Gene link to meningitis infection
By Emma Wilkinson Health reporter, BBC News
Neisseria meningitidis Meningitis is a major cause of death in children worldwide
A set of genes which renders people more prone to meningitis has been pinpointed by researchers.
The international team compared DNA from 1,400 people with bacterial meningitis and 6,000 healthy individuals, Nature Genetics reports.
They found differences in a family of genes involved in the immune response seem to make people more or less susceptible to the infection.
It is hoped the findings will lead to the development of new vaccines.
The researchers were looking at meningitis caused by the Neisseria meningitidis bacterium, which leads to swelling of the lining of the brain and blood poisoning.
It is not the first time researchers have attempted to find out if some people are more likely to catch meningitis because of their genetic make-up.
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This exciting work has thrown new light on factors that play a part in determining why some people get meningococcal disease and others do not”
End Quote Sue Davie Meningitis Trust
But results have previously been unclear, probably because of the small number of people studied.
In the latest study, researchers first scanned the whole genetic code of 475 British patients with meningococcal disease and 4,700 healthy individuals.
They found a clear difference in a small set of genes known to be involved in the immune system response.
When they looked again in two other European populations they found the same result.
The genetic differences found means that, in some people, the bacteria is able to evade the immune system and cause infection, while other people' immune systems are better equipped to fight it off.
The genes encode for a protein called factor H, and factor H related proteins.
Where there are flaws, the meningococcal bacteria is able to bind to these proteins to prevent the immune system from recognising it - almost like a Trojan horse - enabling it to get a foothold.
Study author Professor Michael Levin, an expert in international child health at Imperial College London, said the findings would be particularly useful in developing a vaccine against meningitis B, which is now responsible for most cases in the UK.
There is already an effective vaccine against meningitis C.
"It seems that the genetic differences in factor H between people is what determines susceptibility or resistance.
"It suggests it may be an important protein to include in vaccines, and factor H is already one of the candidates for meningitis B vaccine."
He said the results will also help scientists better tailor vaccines to be effective in the whole population.
It may also open up avenues for improving treatment once people have bacterial meningitis, he said.
Sue Davie, chief executive of the Meningitis Trust, said: "This exciting work has thrown new light on factors that play a part in determining why some people get meningococcal disease and others do not.
"Further work will be needed to establish just what the genetic differences are in the genes which actually cause this susceptibility to invasive infection, but this is a promising start."
What do you think of the findings of this research? Has your family been affected by meningitis? Are you a health professional? Send us your comments using the form below.
Genome-wide association study identifies variants in the CFH region associated with host susceptibility to meningococcal disease
Sonia Davila, Victoria J Wright, Chiea Chuen Khor,
Kar Seng Sim, Alexander Binder, Willemijn B Breunis, David Inwald,
Simon Nadel, Helen Betts, Enitan D Carrol, Ronald de Groot,
Peter W M Hermans, Jan Hazelzet, Marieke Emonts, Chui Chin Lim,
Taco W Kuijpers, Federico Martinon-Torres, Antonio Salas, Werner Zenz,
Michael Levin & Martin L Hibberd for the International Meningococcal Genetics Consortium
Journal name: Nature Genetics
Year published: (2010)
Received 21 January 2010
Accepted 18 July 2010
Published online 08 August 2010
Meningococcal disease is an infection caused by Neisseria meningitidis. Genetic factors contribute to host susceptibility and progression to disease, but the genes responsible for disease development are largely unknown1, 2, 3. We report here a genome-wide association study for host susceptibility to meningococcal disease using 475 individuals with meningococcal disease (cases) and 4,703 population controls from the UK. We performed, in Western European and South European cohorts (consisting of 968 cases and 1,376 controls), two replication studies for the most significant SNPs. A cluster of complement factor SNPs replicated independently in both cohorts, including SNPs within complement factor H (CFH) (rs1065489 (p.936D<E), P = 2.2 × 10−11) and in CFH-related protein 3 (CFHR3)(rs426736, P = 4.6 × 10−13). N. meningitidis is known to evade complement-mediated killing by the binding of host CFH to the meningococcal factor H–binding protein (fHbp)4. Our study suggests that host genetic variation in these regulators of complement activation plays a role in determining the occurrence of invasive disease versus asymptomatic colonization by this pathogen.
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