Polymorphisms in the interleukin-1 gene cluster in children and young adults with systemic meningococcemia.
BACKGROUND
An association has been described between mortality in children with meningococcal disease and functional polymorphisms in the interleukin-1 (IL1) cluster. We undertook a multicenter study to evaluate associations of these polymorphisms in a Central European population.


METHODS
The study involved 95 Middle European pediatric hospitals. We collected blood samples from, and clinical information about, 285 previously healthy children with meningococcal infection. We used a newly developed multiplexed mutagenic separated PCR assay to analyze 6 polymorphisms within the IL1 cluster: IL1A (-889)C/T, IL1A (+4845)G/T, IL1B (-511)C/T, IL1B (-31)C/T, IL1B (+3954), and IL1RA (+2018)C/T. We studied the same polymorphisms in a comparison group of 481 healthy newborns.


RESULTS
Genotype frequencies between patients and the comparison group differed significantly only for the IL1RA (+2018)C/T variant: The CC genotype was more frequent in patients (11%) than in healthy controls (5%; P = 0.008). In the patient group, the C allele was significantly more prevalent (67%) in nonsurvivors than in survivors (42%; P = 0.02).


CONCLUSIONS
The IL1RA (+2018)C/T polymorphism is associated with the risk of meningococcal disease and with its outcome.
Endler
Georg
G
Department of General Pediatrics, Medical University of Graz, Graz, Austria.
Marculescu
Rodrig
R
Starkl
Philipp
P
Binder
Alexander
A
Geishofer
Gotho
G
Müller
Martin
M
Zöhrer
Bettina
B
Resch
Bernhard
B
Zenz
Werner
W
Mannhalter
Christine
C
D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D005060:Europe; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007375:Interleukin-1 / Q000235:genetics*; D008297:Male; D008589:Meningococcal Infections / Q000235:genetics / Q000276:immunology*; D005810:Multigene Family; D011110:Polymorphism, Genetic; D044465:White People
D007375:Interleukin-1