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.
| Original language | English |
|---|---|
| Pages (from-to) | 1557-1560 |
| Number of pages | 4 |
| Journal | Journal of Infectious Diseases |
| Volume | 182 |
| Issue number | 5 |
| DOIs | |
| Publication status | Published - 2000 |
| Externally published | Yes |
Bibliographical note
Funding Information:Received 5 June 2000; revised 19 July 2000; electronically published 9 October 2000. Presented in part: 39th Interscience Conference on Antimicrobial Agents and Chemotherapy, San Francisco, 26–29 September 1999 (abstract 496). This study was approved by the Research Ethics Committee of the Public Health Laboratory Service for England and Wales. Financial support: Special Trustees for the Former United Sheffield Hospitals (grant 87753); Ralph Sutcliffe Fund; National Meningitis Trust. a Present affiliation: Genetic Research, Intermountain Health Care, Salt Lake City, Utah. Reprints or correspondence: Dr. Robert C. Read, Infection and Immunity, Division of Molecular and Genetic Medicine, F Fl., University of Sheffield Medical School, Beech Hill Rd., Sheffield S10 2RX, United Kingdom ([email protected]).
