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

R C Read1, N J Camp, F S di Giovine

  • 11Division 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

The Journal of Infectious Diseases
|October 7, 2000
PubMed

Insights

Interleukin-1 (IL-1) gene variants are linked to severe meningococcal disease outcomes. Specific IL-1B genotypes increase the risk of death, while a combined IL-1 genotype is associated with survival.

Area of Science:

  • Genetics and immunology
  • Infectious disease research
  • Molecular biology

Background:

  • Meningococcal disease, caused by Neisseria meningitidis, can lead to severe outcomes.
  • Genetic factors may influence disease severity and host response.
  • Interleukin-1 (IL-1) and Tumor Necrosis Factor (TNF) are key inflammatory cytokines.

Purpose of the Study:

  • To investigate the association between genetic variants in IL-1 and TNF gene families and the severity of meningococcal disease.
  • To identify specific genotypes that correlate with fatal outcomes or survival in patients with meningococcal infections.

Main Methods:

  • Genotyping of 276 patients with microbiologically confirmed Neisseria meningitidis infection.
  • Analysis of known variants in the IL-1B, IL-1RN, and TNF gene families.
  • Statistical analysis to determine associations between genotypes and mortality or survival rates.

Main Results:

  • A significant association was found between fatal outcome and genotype at IL1B (nucleotide position -511) (P<.001).
  • Homozygosity for IL1B (-511) alleles (1/1 and 2/2) showed increased odds ratios for death compared to heterozygotes (1/2).
  • A composite genotype (IL1B heterozygosity and IL1RN homozygosity) was significantly associated with survival (P=.018).
  • No association was observed between TNF genotype and fatal outcome.

Conclusions:

  • IL-1 gene variants, particularly at the IL1B (-511) locus, significantly influence the severity of meningococcal disease.
  • Specific IL-1 genotypes are predictive of mortality risk, while others are linked to better survival.
  • Genetic predisposition related to IL-1 cytokine pathways plays a crucial role in meningococcal disease pathogenesis.

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