A Functional Polymorphism of Toll-like Receptor 4 Is Not Associated with Likelihood or Severity of Meningococcal Disease

• Published in: The Journal of infectious diseases Vol. 184; no. 5; pp. 640 - 642
• Main Authors: Read, Robert C., Pullin, Jodie, Gregory, Simone, Borrow, Raymond, Kaczmarski, Edward B., di Giovine, Francesco S., Dower, Steven K., Cannings, Chris, Wilson, Anthony G.
• Format: Journal Article
• Language: English
• Published: Chicago, IL The University of Chicago Press 01.09.2001; University of Chicago Press
• Subjects: Adolescent; Adult; Aged; Alleles; Bacterial diseases; Bacterial diseases of the nervous system. Bacterial myositis; Biological and medical sciences; Blood donation; Child; Child, Preschool; Concise Comunications; Cytokines; Disease susceptibility; Diseases; Drosophila Proteins; Epithelial cells; Gene Frequency; Genetic Predisposition to Disease; Genotype; Genotypes; Human bacterial diseases; Human protozoal diseases; Humans; Infant; Infant, Newborn; Infections; Infectious diseases; Malaria; Medical sciences; Membrane Glycoproteins - genetics; Membrane Glycoproteins - metabolism; Meningococcal Infections - genetics; Meningococcal Infections - immunology; Meningococcal Infections - microbiology; Middle Aged; Neisseria meningitidis - metabolism; Parasitic diseases; Polymorphism, Genetic - genetics; Protozoal diseases; Receptors, Cell Surface - genetics; Receptors, Cell Surface - metabolism; Severity of Illness Index; Standardized tests; Toll like receptors; Toll-Like Receptor 4; Human; Neisseriaceae; Cytokine; Neisseria meningitidis; Blood; Infection; Allele; Sensitivity; Gene; Bacteriosis; Lipopolysaccharide; Bacteria; Micrococcales; Age; Release; Blood donor; Meningococcal disease; Polymorphism
• ISSN: 0022-1899; 1537-6613
• DOI: 10.1086/322798

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