title: A functional polymorphism of toll-like receptor 4 is not associated with likelihood or severity of meningococcal disease.
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.
authors.affiliation: Division of Genomic Medicine, Royal Hallamshire Hospital, University of Sheffield, Sheffield S10 2RX, United Kingdom. r.c.read@shef.ac.uk
authors.forename: R C
authors.initials: RC
authors.lastname: Read
authors.forename: J
authors.initials: J
authors.lastname: Pullin
authors.forename: S
authors.initials: S
authors.lastname: Gregory
authors.forename: R
authors.initials: R
authors.lastname: Borrow
authors.forename: E B
authors.initials: EB
authors.lastname: Kaczmarski
authors.forename: F S
authors.initials: FS
authors.lastname: di Giovine
authors.forename: S K
authors.initials: SK
authors.lastname: Dower
authors.forename: C
authors.initials: C
authors.lastname: Cannings
authors.forename: A G
authors.initials: AG
authors.lastname: Wilson
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002648:Child; D002675:Child, Preschool; D029721:Drosophila Proteins; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008562:Membrane Glycoproteins / Q000235:genetics* / Q000378:metabolism; D008589:Meningococcal Infections / Q000235:genetics / Q000276:immunology* / Q000382:microbiology; D008875:Middle Aged; D009345:Neisseria meningitidis / Q000378:metabolism*; D011110:Polymorphism, Genetic / Q000235:genetics*; D011956:Receptors, Cell Surface / Q000235:genetics* / Q000378:metabolism; D012720:Severity of Illness Index; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors
chemical_list: D029721:Drosophila Proteins; D008562:Membrane Glycoproteins; D011956:Receptors, Cell Surface; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors