Genetic polymorphism of the binding domain of surfactant protein-A2 increases susceptibility to meningococcal disease
Genetic polymorphism of the binding domain of surfactant protein-A2 increases susceptibility to meningococcal disease
BACKGROUND: Meningococcal disease occurs after colonization of the nasopharynx with Neisseria meningitidis. Surfactant protein (SP)-A and SP-D are pattern-recognition molecules of the respiratory tract that activate inflammatory and phagocytic defences after binding to microbial sugars. Variation in the genes of the surfactant proteins affects the expression and function of these molecules.
METHODS: Allele frequencies of SP-A1, SP-A2, and SP-D were determined by polymerase chain reaction in 303 patients with microbiologically proven meningococcal disease, including 18 patients who died, and 222 healthy control subjects.
RESULTS: Homozygosity of allele 1A1 of SP-A2 increased the risk of meningococcal disease (odds ratio [OR], 7.4; 95% confidence interval [CI], 1.3-42.4); carriage of 1A5 reduced the risk (OR, 0.3; 95% CI, 0.1-0.97). An analysis of the multiple single-nucleotide polymorphisms in SP-A demonstrated that homozygosity for alleles encoding lysine (in 1A1) rather than glutamine (in 1A5) at amino acid 223 in the carbohydrate recognition domain was associated with an increased risk of meningococcal disease (OR, 6.7; 95% CI, 1.4-31.5). Carriage of alleles encoding lysine at residue 223 was found in 61% of patients who died, compared with 35% of those who survived (OR adjusted for age, 2.9; 95% CI, 1.1-7.7). Genetic variation of SP-A1 and SP-D was not associated with meningococcal disease.
CONCLUSIONS: Gene polymorphism resulting in the substitution of glutamine with lysine at residue 223 in the carbohydrate recognition domain of SP-A2 increases susceptibility to meningococcal disease, as well as the risk of death.
Adult, Aged, Alleles, Amino Acid Substitution, Binding Sites, Case-Control Studies, Child, Child, Preschool, Genetic Predisposition to Disease, Haplotypes, Humans, Infant, Infant, Newborn, Meningococcal Infections, Middle Aged, Odds Ratio, Polymorphism, Genetic, Protein Structure, Tertiary, Pulmonary Surfactant-Associated Protein A, Pulmonary Surfactant-Associated Protein D, Journal Article, Research Support, Non-U.S. Gov't
1426-1433
Jack, Dominic L.
246dc47b-5b5e-4933-9227-d13aafd9cb88
Cole, Joby
546f9b85-70c2-4f0b-9915-aa2b2016804f
Naylor, Simone C.
d0233f03-8cc1-445d-ad95-9d4bacb16f6c
Borrow, Raymond
dd28679e-2072-4639-9d68-851ada2eeea3
Kaczmarski, Edward B.
b64d93b8-aaee-44f6-a7a3-715f8971d3b3
Klein, Nigel J.
f01b50e5-cb25-4558-99aa-b697d534fb55
Read, Robert C.
b5caca7b-0063-438a-b703-7ecbb6fc2b51
1 December 2006
Jack, Dominic L.
246dc47b-5b5e-4933-9227-d13aafd9cb88
Cole, Joby
546f9b85-70c2-4f0b-9915-aa2b2016804f
Naylor, Simone C.
d0233f03-8cc1-445d-ad95-9d4bacb16f6c
Borrow, Raymond
dd28679e-2072-4639-9d68-851ada2eeea3
Kaczmarski, Edward B.
b64d93b8-aaee-44f6-a7a3-715f8971d3b3
Klein, Nigel J.
f01b50e5-cb25-4558-99aa-b697d534fb55
Read, Robert C.
b5caca7b-0063-438a-b703-7ecbb6fc2b51
Jack, Dominic L., Cole, Joby, Naylor, Simone C., Borrow, Raymond, Kaczmarski, Edward B., Klein, Nigel J. and Read, Robert C.
(2006)
Genetic polymorphism of the binding domain of surfactant protein-A2 increases susceptibility to meningococcal disease.
Clinical Infectious Diseases, 43 (11), .
(doi:10.1086/508775).
Abstract
BACKGROUND: Meningococcal disease occurs after colonization of the nasopharynx with Neisseria meningitidis. Surfactant protein (SP)-A and SP-D are pattern-recognition molecules of the respiratory tract that activate inflammatory and phagocytic defences after binding to microbial sugars. Variation in the genes of the surfactant proteins affects the expression and function of these molecules.
METHODS: Allele frequencies of SP-A1, SP-A2, and SP-D were determined by polymerase chain reaction in 303 patients with microbiologically proven meningococcal disease, including 18 patients who died, and 222 healthy control subjects.
RESULTS: Homozygosity of allele 1A1 of SP-A2 increased the risk of meningococcal disease (odds ratio [OR], 7.4; 95% confidence interval [CI], 1.3-42.4); carriage of 1A5 reduced the risk (OR, 0.3; 95% CI, 0.1-0.97). An analysis of the multiple single-nucleotide polymorphisms in SP-A demonstrated that homozygosity for alleles encoding lysine (in 1A1) rather than glutamine (in 1A5) at amino acid 223 in the carbohydrate recognition domain was associated with an increased risk of meningococcal disease (OR, 6.7; 95% CI, 1.4-31.5). Carriage of alleles encoding lysine at residue 223 was found in 61% of patients who died, compared with 35% of those who survived (OR adjusted for age, 2.9; 95% CI, 1.1-7.7). Genetic variation of SP-A1 and SP-D was not associated with meningococcal disease.
CONCLUSIONS: Gene polymorphism resulting in the substitution of glutamine with lysine at residue 223 in the carbohydrate recognition domain of SP-A2 increases susceptibility to meningococcal disease, as well as the risk of death.
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More information
Accepted/In Press date: 31 July 2006
e-pub ahead of print date: 1 December 2006
Published date: 1 December 2006
Keywords:
Adult, Aged, Alleles, Amino Acid Substitution, Binding Sites, Case-Control Studies, Child, Child, Preschool, Genetic Predisposition to Disease, Haplotypes, Humans, Infant, Infant, Newborn, Meningococcal Infections, Middle Aged, Odds Ratio, Polymorphism, Genetic, Protein Structure, Tertiary, Pulmonary Surfactant-Associated Protein A, Pulmonary Surfactant-Associated Protein D, Journal Article, Research Support, Non-U.S. Gov't
Identifiers
Local EPrints ID: 416316
URI: http://eprints.soton.ac.uk/id/eprint/416316
ISSN: 1058-4838
PURE UUID: 72d8dc18-d141-4915-80c8-90cb3dbb21a9
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Date deposited: 12 Dec 2017 17:30
Last modified: 16 Mar 2024 04:10
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Author:
Dominic L. Jack
Author:
Joby Cole
Author:
Simone C. Naylor
Author:
Raymond Borrow
Author:
Edward B. Kaczmarski
Author:
Nigel J. Klein
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