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.
%0 Journal Article
%1 read_functional_2001
%A Read, R C
%A Pullin, J
%A Gregory, S
%A Borrow, R
%A Kaczmarski, E B
%A di Giovine, F S
%A Dower, S K
%A Cannings, C
%A Wilson, A G
%D 2001
%J The Journal of Infectious Diseases
%K 4, Adolescent, Adult, Aged, Cell Child, Disease, Drosophila Frequency, Gene Genetic Genetic, Genotype, Glycoproteins, Humans, Illness Index, Infant, Infections, Membrane Meningococcal Middle Neisseria Newborn, Polymorphism, Predisposition Preschool, Proteins, Receptor Receptors Receptors, Severity Surface, meningitidis, of to {Toll-Like}
%N 5
%P 640--2
%R 10.1086/322798
%T A functional polymorphism of toll-like receptor 4 is not associated with likelihood or severity of meningococcal disease
%U http://www.ncbi.nlm.nih.gov/pubmed/11494169
%V 184
%X 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.
@article{read_functional_2001,
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.},
added-at = {2011-03-11T10:05:34.000+0100},
author = {Read, R C and Pullin, J and Gregory, S and Borrow, R and Kaczmarski, E B and di Giovine, F S and Dower, S K and Cannings, C and Wilson, A G},
biburl = {https://www.bibsonomy.org/bibtex/2bd4783adcf3a4c6c6d519164105785fe/jelias},
doi = {10.1086/322798},
interhash = {b121b5b6396682f704e657a3f5263a90},
intrahash = {bd4783adcf3a4c6c6d519164105785fe},
issn = {0022-1899},
journal = {The Journal of Infectious Diseases},
keywords = {4, Adolescent, Adult, Aged, Cell Child, Disease, Drosophila Frequency, Gene Genetic Genetic, Genotype, Glycoproteins, Humans, Illness Index, Infant, Infections, Membrane Meningococcal Middle Neisseria Newborn, Polymorphism, Predisposition Preschool, Proteins, Receptor Receptors Receptors, Severity Surface, meningitidis, of to {Toll-Like}},
month = sep,
note = {{PMID:} 11494169},
number = 5,
pages = {640--2},
timestamp = {2011-03-11T10:06:30.000+0100},
title = {A functional polymorphism of toll-like receptor 4 is not associated with likelihood or severity of meningococcal disease},
url = {http://www.ncbi.nlm.nih.gov/pubmed/11494169},
volume = 184,
year = 2001
}