Gene May Affect Meningitis

Children with a genetic predisposition to produce high concentrations of a blood-clotting enzyme linked to meningitis are twice as likely to die from the severe form of that disease as other children, new research says.

The findings do not indicate that genetics influence the chances of contracting meningococcal disease, but rather that those who get it are more likely to progress to deadly septic shock.

The research is published in two separate studies in this week's issue of The Lancet, a British medical journal.

Meningococcal disease, which particularly affects young children, throws the blood's clotting mechanisms out of balance. It is relatively rare, afflicting about one in 100,000 people. It is fatal in about one in 10 of those cases.

Meningitis infects the lining around the brain and spinal column. In about 20 percent of cases, the infection is particularly severe, causing septic shock resulting from toxins released by the bacteria. About 20 percent to 40 percent of people stricken with that form die.

It is usually assumed that an infection's virulence is linked to the bacterium, rather than the host, said Dr. Bruce Beutler, a meningitis expert at the University of Texas Southwestern Medical Center who was not connected with the research.

These new findings pave the way for genetically testing people to determine how they are likely to fare if they contract bacterial infections, he said.

In the two studies, two groups of British and Dutch scientists examined a gene that produces a blood-clotting enzyme called PAI-1 that is found in high amounts in people with meningococcal disease.

It is not known whether the elevated levels are the result of the disease or a cause. These studies are the first to link the gene responsible for producing the enzyme with the disease, Beutler said.

The research focused on examining the three variations of the gene. Those include 4G/4G, where both the mother and the father pass on a gene type called a 4G.

The first study, by scientists at London's Imperial College of Medicine and Rotterdam's Sophia Children's Hospital, involved 175 children with meningococcal disease and 226 healthy boys and girls.

It found that, in the severe cases involving toxic shock, the children who carried the same genes from each parent were twice as likely to die as those who had one of the other two variations. Those children also had higher concentrations of the PAI-1 enzyme in their blood.

Those who died of the disease -- whether they had the 4G/4G combination or not -- also had higher concentrations of the enzyme than the children who survived.

The scientists noted, however, that the 4G/4G combination also was found among the healthy children in their study -- proportionally about as frequently as among the sick children.

This suggests that having that gene combination does not pose any increased risk of contracting meningococcal disease, the study said.

Dr. Martin Hibberd of Lodon's Imperial College, the first study's lead author, said that having the 4G/4G combination does not necessarily spell doom.

"People shouldn't think they've got a genetic defect," he said. "In another disease, the 4G/4G variation may be of benefit."

The second research team at Leiden University in the Netherlands agreed. They found, however, that if children got the disease, those with the 4G/4G gene variation fared worse.

They studied 183 immediate relatives of children with meningococcal disease. The 4G/4G gene combination was present in only 9 percent of the families of children who got meningitis, but in 36 percent of the families of children with septic shock. Children whose relatives carried the 4G/4G gene type were six times more likely to develop septic shock.

Written By Emma Ross