Variation within Genes Encoding Interleukin-1 and the Interleukin-1 Receptor Antagonist Influence the Severity of Meningococcal Disease

Background: Genetically determined variation in proinflammatory cytokine release influences severity of meningococcal disease and other serious infections. Objective: To ascertain the relative frequencies of single nucleotide polymorphisms within the interleukin-1 gene locus among patients who survived and those who died of meningococcal disease and a control population of blood donors. Design: Association study. Setting: England and Wales. Patients: 1106 consecutively received blood samples from persons with microbiologically confirmed meningococcal disease and 839 samples from blood donors. Measurements: Patient demographic and outcome data, infecting meningococcal serogroups, and genotype at the IL1B-511) and IL1RN(+2018) loci of patients and blood donor controls. Results: Genotype frequency did not differ between patients with meningococcal disease and blood donor controls. Logistic regression analysis revealed that the likelihood of death was significantly influenced by age but not socioeconomic status and was higher in patients who were infected with serogroup C (odds ratio for survival, 0.50 [95% Cl, 0.33 to 0.78]). Patients carrying the common allele at (IL18(-511) were more likely to survive (odds ratio, 2.01 [CI, 1.11 to 3.79]). Patients with this allele were less likely to survive if they also carried the rare allele at IL1RN(+2018) (odds ratio, 0.61 [CI, 0.38 to 0.993]). Conclusion: Genotype at the interleukin-1 gene locus influences likelihood of survival of meningococcal disease but has no effect on susceptibility to the infection. Increasing age and infection with serogroup C also influence the likelihood of death.