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Research Uncovers Genetic Basis For Meningococcal Septic Shock LONDON, ON -- August 13, 1999 -- The bacterium Neisseria meningitidis commonly causes meningitis. However, in some people, it can cause a severe disorder-meningococcal septic shock-that involves inappropriate blood clotting and multiorgan failure. Two groups of researchers, who report their findings in this week’s Lancet, have discovered that there may be a genetic basis for the development of septic shock, and that people with this genetic trait are more likely to die of the disease than those without the trait. The investigators studied a polymorphism (slight genetic variation) in a gene which codes for an enzyme (plasminogen-activator-inhibitor-1 [PAI-1]) involved in the formation of blood clots. This polymorphism creates three different combinations of the gene (genotypes)-4G/4G, 4G/5G, and 5G/5G. Dr. Peter Hermans and colleagues, from Sophia Children’s Hospital, Rotterdam, Netherlands, and the Imperial College School of Medicine, UK, studied 175 children with N meningitidis infection. They found that children with the 4G/4G genotype had significantly higher PAI-1 concentrations than those with the other genotypes, and had an increased risk of death. In another report, Dr. Rudi Westendorp and colleagues, from the Leiden University Medical Centre, Leiden, Netherlands, studied the PAI-1 genotypes of 183 first-degree relatives of patients with N meningitidis infection. They found that 31 (36 percent) of 85 relatives of patients with septic shock had the 4G/4G genotype, compared with only 4 (9 percent) of 45 relatives of those with meningitis. Patients whose relatives had the 4G/4G genotype had a six-fold higher risk of developing septic shock than meningitis. The researchers conclude that a genetic predisposition to produce high concentrations of the enzyme PAI-1 is associated with the development of septic shock in patients with N meningitidis infection. Therefore, “measures to reduce the concentration of PAI-1... may be beneficial in treating the disease.” E-mail this page to a friend or colleague! To print, use this version