A functional polymorphism of Toll-like receptor 4 is not associated with likelihood or severity of meningococcal disease

Robert C. Read, Jodie Pullin, Simone Gregory, Raymond Borrow, Edward B. Kaczmarski, Francesco S. Di Giovine, Steven K. Dower, Chris Cannings, Anthony G. Wilson

Research output: Contribution to journalArticlepeer-review

176 Citations (Scopus)

Abstract

Human Toll-like receptor 4 (TLR4) transduces proinflammatory cytokine release by human cells in response to lipopolysaccharide (LPS). This study tested the hypothesis that, if TLR4 is rate limiting for a successful response to bacterial LPS in humans, a human gene polymorphism that results in the amino acid substitution Asp299Gly and causes reduced expression and function of TLR4 should influence susceptibility to or severity of natural gram-negative infection. The allele frequency of the Asp299Gly polymorphism was 5.9% among 879 blood donors, 6.5% among 1047 patients with microbiologically proven meningococcal disease, and 4.1% among 86 patients who died of meningococcal disease. No significant differences were observed, including those analyzed after stratification of the infected population by age and by meningococcal serogroup. Therefore, this functional TLR4 polymorphism does not influence susceptibility to or severity of meningococcal disease.

Original languageEnglish
Pages (from-to)640-642
Number of pages3
JournalJournal of Infectious Diseases
Volume184
Issue number5
DOIs
Publication statusPublished - 1 Sept 2001
Externally publishedYes

Bibliographical note

Funding Information:
Received 3 April 2001; revised 15 May 2001; electronically published 30 July 2001. This study was approved by the Research Ethics Committee of the Public Health Laboratory Service for England and Wales. Financial support: Wellcome Trust; Meningitis Research Foundation. Reprints or correspondence: Dr. R. C. Read, Division of Genomic Medicine, University of Sheffield Medical School, Beech Hill Rd., Sheffield S10 2RX, United Kingdom (r.c.read@shef.ac.uk).

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