title: An interleukin-1 genotype is associated with fatal outcome of meningococcal disease.
abstract: To determine whether known variants of the interleukin-1 (IL-1) and tumor necrosis factor (TNF) gene families are associated with severe manifestations of meningococcal disease, 276 white patients 4-70 years of age (median, 17 years) were genotyped. All patients had microbiologically proven Neisseria meningitidis infection; 39 died and 237 survived. A significant association (P<.001) was found between fatal outcome and genotype at IL1B (nucleotide position -511). Homozygous individuals, both for the common (1/1) and the rare (2/2) alleles, had increased odds ratios (ORs) for death, compared with heterozygous individuals (1/2): ORs (95% confidence intervals [CIs]) were 3.39 (1.39-8.29) and 7.35 (2.51-21.45), respectively. The mortality rates according to genotype at IL1B (-511) were 18.0% (1/1), 6.1% (1/2), and 32.3% (2/2), compared with 14.2% overall. The composite genotype, consisting of heterozygosity of IL1B (-511) together with homozygosity of the common allele of the IL-1 receptor antagonist gene (IL1RN) at +2018, was significantly associated with survival (P=.018; OR, 7.78 [95% CI, 1. 05-59.05]). There was no association between TNF genotype and fatal outcome. These data suggest that IL-1 genotype influences the severity of meningococcal disease.
authors.affiliation: 1Division of Genomic Medicine, University of Sheffield Medical School, Sheffield, and 2Meningococcal Reference Unit, Manchester Public Health Laboratory, Withington Hospital, Manchester, United Kingdom. r.c.read@sheffield.ac.uk
authors.forename: R C
authors.initials: RC
authors.lastname: Read
authors.forename: N J
authors.initials: NJ
authors.lastname: Camp
authors.forename: F S
authors.initials: FS
authors.lastname: di Giovine
authors.forename: R
authors.initials: R
authors.lastname: Borrow
authors.forename: E B
authors.initials: EB
authors.lastname: Kaczmarski
authors.forename: A G
authors.initials: AG
authors.lastname: Chaudhary
authors.forename: A J
authors.initials: AJ
authors.lastname: Fox
authors.forename: G W
authors.initials: GW
authors.lastname: Duff
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002648:Child; D002675:Child, Preschool; D005838:Genotype; D006801:Humans; D007375:Interleukin-1 / Q000235:genetics*; D008589:Meningococcal Infections / Q000235:genetics / Q000401:mortality*; D008875:Middle Aged; D011110:Polymorphism, Genetic; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
chemical_list: D007375:Interleukin-1; D014409:Tumor Necrosis Factor-alpha