Polymorphisms in the Interleukin-1 Gene Cluster in Children and Young Adults with Systemic Meningococcemia

Abstract

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. Patients and 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). Conclusion: The IL1RA (؉2018)C/T polymorphism is associated with the risk of meningococcal disease and with its outcome.

Common Variants in Interleukin-1-Beta Gene Are Associated with Intracranial Hemorrhage and Susceptibility to Brain Arteriovenous Malformation

“…As a sensitivity analysis, we conducted a random effects meta-analysis to validate our case-control findings using the pooled IL-1β –31 CC genotype frequency of Caucasian controls from 14 published studies [17,18,19,20,21,22,23,24,25,26,27,28,29,30]. A restricted maximum likelihood method was used to estimate the between-study variance as implemented in the Stata metareg package [31].…”

Hierarchical genomic analysis of carried and invasive serogroup A Neisseria meningitidis during the 2011 epidemic in Chad

“…The MDA island genes were present in both Clusters 1 and 2 with the same alleles and thus could not explain the differentiation seen in this collection of isolates. Host genetic polymorphisms affecting the susceptibility of an individual to invasive meningococcal disease have been described, such as those in complement components such as factor H [37] or C6 deficiencies known to vary depending on the racial group and described as more common in African-American in the USA [38], interleukin-1 gene cluster [39] or the plasminogen activator inhibitor 1 [40]. Differences in host genetics could also explain our clusters; however, such studies have yet to be undertaken in African subjects.…”

Genetic variation of innate immune response genes in invasive pneumococcal and meningococcal disease applied to the pathogenesis of meningitis

“…more likely to survive and significantly less likely to survive if they also carried the rare allele at the IL-1 receptor antagonist gene IL1RN þ 2018. In another study, this SNP was also associated with susceptibility and mortality of MD, 129 while no association was found in five other SNPs in IL1A and IL1B. Severity and mortality of MD was associated with IL6-174 G/G and IL10-1082 A/A, but not with LTA þ 252, TNF-308, IL10-592, or IL1b SNPs.…”