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

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

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.

Adolescent, Adult, Aged, Child, Child, Preschool, Drosophila Proteins, Gene Frequency, Genetic Predisposition to Disease, Genotype, Humans, Infant, Infant, Newborn, Membrane Glycoproteins, Meningococcal Infections, Middle Aged, Neisseria meningitidis, Polymorphism, Genetic, Receptors, Cell Surface, Severity of Illness Index, Toll-Like Receptor 4, Toll-Like Receptors, Journal Article, Research Support, Non-U.S. Gov't
0022-1899
640-642
Read, R.C.
b5caca7b-0063-438a-b703-7ecbb6fc2b51
Pullin, J.
4c0fa15e-1ba7-49c4-bfc6-f46944951a9f
Gregory, S.
bd6cbd35-ec44-4cf7-bf2b-f2a4b398fa52
Borrow, R.
ae200ab8-f9f3-49c6-a161-c8fc31d00a58
Kaczmarski, E.B.
b64d93b8-aaee-44f6-a7a3-715f8971d3b3
di Giovine, F.S.
56266edf-877e-424e-adaf-07b7580c2b90
Dower, S.K.
c59b6ed1-57d4-49cb-815c-038a96601ecc
Cannings, C.
1d53c1b0-35b7-42ea-ab2a-b75723ef26d3
Wilson, A.G.
bfb38928-47c3-46aa-a09e-2501b60d752e
Read, R.C.
b5caca7b-0063-438a-b703-7ecbb6fc2b51
Pullin, J.
4c0fa15e-1ba7-49c4-bfc6-f46944951a9f
Gregory, S.
bd6cbd35-ec44-4cf7-bf2b-f2a4b398fa52
Borrow, R.
ae200ab8-f9f3-49c6-a161-c8fc31d00a58
Kaczmarski, E.B.
b64d93b8-aaee-44f6-a7a3-715f8971d3b3
di Giovine, F.S.
56266edf-877e-424e-adaf-07b7580c2b90
Dower, S.K.
c59b6ed1-57d4-49cb-815c-038a96601ecc
Cannings, C.
1d53c1b0-35b7-42ea-ab2a-b75723ef26d3
Wilson, A.G.
bfb38928-47c3-46aa-a09e-2501b60d752e

Read, R.C., Pullin, J., Gregory, S., Borrow, R., Kaczmarski, E.B., di Giovine, F.S., Dower, S.K., Cannings, C. and Wilson, A.G. (2001) A functional polymorphism of toll-like receptor 4 is not associated with likelihood or severity of meningococcal disease. The Journal of Infectious Diseases, 184 (5), 640-642. (doi:10.1086/322798).

Record type: Article

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.

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More information

Published date: 1 September 2001
Keywords: Adolescent, Adult, Aged, Child, Child, Preschool, Drosophila Proteins, Gene Frequency, Genetic Predisposition to Disease, Genotype, Humans, Infant, Infant, Newborn, Membrane Glycoproteins, Meningococcal Infections, Middle Aged, Neisseria meningitidis, Polymorphism, Genetic, Receptors, Cell Surface, Severity of Illness Index, Toll-Like Receptor 4, Toll-Like Receptors, Journal Article, Research Support, Non-U.S. Gov't

Identifiers

Local EPrints ID: 416856
URI: https://eprints.soton.ac.uk/id/eprint/416856
ISSN: 0022-1899
PURE UUID: b44c1b6a-7284-4f77-8dc6-7a8f5936a21a
ORCID for R.C. Read: ORCID iD orcid.org/0000-0002-4297-6728

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Date deposited: 11 Jan 2018 17:30
Last modified: 31 Jul 2019 00:35

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Contributors

Author: R.C. Read ORCID iD
Author: J. Pullin
Author: S. Gregory
Author: R. Borrow
Author: E.B. Kaczmarski
Author: F.S. di Giovine
Author: S.K. Dower
Author: C. Cannings
Author: A.G. Wilson

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