There is evidence that a number of genetic factors can influence susceptibility to, and severity of meningococcal disease. Knowledge of the genetic determinants of outcome of meningococcal infection will help us determine the pathophysiology, and ultimately therapies for meningococcal disease and other related severe infections. We have preliminary data which suggest that an interleukin-1 genotype influences the outcome of meningococcal disease. In this study, we will collect DNA extracted from whole blood from approximately 1,300 patients with microbiologically proven meningococcal disease, and establish a database of clinical outcome information related to each sample. The sample will include DNA from approximately 100 patients who died, and it is expected that 14%, 11% and 4% will have experienced the complications of subjective hearing loss, subjective visual impairment and loss of limbs, digits or cuticle, respectively. Samples will then be anonymised prior to genotyping at TNF and IL-1 polymorphic loci. The representation of TNF and IL-1 gene polymorphisms amongst fatal cases, survivors with complications and survivors without complications will then be compared. The DNA collection and database will be available for other investigator, subject to ethical/quality considerations.
Results from this study have been published in scientific journals as follows:
Read RC, Pullin J, Gregory S, Borrow R, Kaczmarski EB, di Giovine FS, Dower SK, Cannings C, Wilson AG.
A functional polymorphism of toll-like receptor 4 is not associated with likelihood or severity of meningococcal disease.
J Infect Dis 2001 Sep 1;184(5):640-2. Epub 2001 Jul 30. http://www.journals.uchicago.edu/JID/journal/issues/v184n5/010377/010377.web.pdf
Townsend R, Goodwin L, Stevanin TM, Silcocks PB, Parker A, Maiden MC, Read RC.
Invasion by Neisseria meningitidis varies widely between clones and among nasopharyngeal mucosae derived from adult human hosts.
Microbiology 2002 May;148(Pt 5):1467-74.
Read RC, Cannings C, Naylor SC, Timms JM, Maheswaran R, Borrow R, Kaczmarski EB, Duff GW.
Variation within genes encoding interleukin-1 and the interleukin-1 receptor antagonist influence the severity of meningococcal disease.
Ann Intern Med 2003 Apr 1;138(7):534-41.