An interleukin-1 genotype is associated with fatal outcome of meningococcal disease

To determine whether known variants of the interleukin-1 (IL-1) and tumor n ecrosis factor (TNF) gene families are associated with severe manifestation s of meningococcal disease, 276 white patients 4-70 years of age (median, 1 7 years) were genotyped. All patients had microbiologically proven Neisseri a meningitidis infection; 39 died and 237 survived. A significant associati on (P < .001) was found between fatal outcome and genotype at IL1B (nucleot ide position -511). Homozygous individuals, both for the common (1/1) and t he rare (2/2) alleles, had increased odds ratios (ORs) for death, compared with heterozygous individuals (1/2): ORs (95% confidence intervals [CIs]) w ere 3.39 (1.39-8.29) and 7.35 (2.51-21,45), respectively. The mortality rat es according to genotype at IL1B(-511) were 18.0% (111), 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 a llele of the IL-1 receptor antagonist gene (IL1RN) at +2018, was significan tly associated with survival (P = .018; OR, 7.78 [95% CI, 1.05-59,05]). The re was no association between TNF genotype and fatal outcome. These data su ggest that IL-1 genotype influences the severity of meningococcal disease.