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Haplotypic diversity in human CEACAM genes: effects on susceptibility to meningococcal disease

Haplotypic diversity in human CEACAM genes: effects on susceptibility to meningococcal disease
Haplotypic diversity in human CEACAM genes: effects on susceptibility to meningococcal disease
Adhesion between the opacity-associated adhesin (Opa) proteins of Neisseria meningitidis and human carcino-embryonic antigen cell adhesion molecule (CEACAM) proteins is an important stage in the pathogenesis of meningococcal disease, a globally important bacterial infection. Most disease is caused by a small number of meningococcal genotypes known as hyperinvasive lineages. As these are also carried asymptomatically, acquisition of them alone cannot explain why only some hosts develop meningococcal disease. Our aim was to determine whether genetic diversity in CEACAM is associated with susceptibility to meningococcal disease. Frequency distributions of alleles, genotypes and haplotypes were compared in four CEACAM genes in 384 case samples and 190 controls. Linkage disequilibrium among polymorphic sites, haplotype structures and relationships were also analysed. A number of polymorphisms were observed in CEACAM genes but the diversity of CEACAM1, to which most Opa proteins bind, was lower, and a small number of high-frequency haplotypes were detected. Dose-dependent associations of three CEACAM haplotypes with meningococcal disease were observed, with the effect of carrying these haplotypes amplified in homozygous individuals. Two haplotypes were protective while one haplotype in CEACAM6 was associated with a twofold increase in disease susceptibility. These data imply that human CEACAM may be one determinant of human susceptibility to meningococcal disease
ceacam, snp, haplotype, meningococcal, susceptibility
1466-4879
30-37
Callaghan, M.J.
8147cabf-e95f-4e1c-a7cf-06a0182f8cdf
Rockett, K.
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Banner, C.
d8320705-2117-4e7c-bf89-9a85f9955c72
Haralambous, E.
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Betts, H.
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Faust, S.
f97df780-9f9b-418e-b349-7adf63e150c1
Maiden, M.C.J.
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Kroll, J. S.
ff3ca6a4-37e0-4d56-a572-e11c4674106d
Levin, M.
3668029d-82f9-422c-8a69-42ccae2e88bf
Kwiatkowski, D.P.
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Pollard, A.J.
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Callaghan, M.J.
8147cabf-e95f-4e1c-a7cf-06a0182f8cdf
Rockett, K.
0a0909cf-2327-4452-a319-8d43daa96855
Banner, C.
d8320705-2117-4e7c-bf89-9a85f9955c72
Haralambous, E.
7b8fabad-9021-4602-8744-24eb76d5662f
Betts, H.
0506cae1-f0aa-4ee5-a85c-0e368838e797
Faust, S.
f97df780-9f9b-418e-b349-7adf63e150c1
Maiden, M.C.J.
9843f24e-6b60-4a28-90d3-ae52d3fe158a
Kroll, J. S.
ff3ca6a4-37e0-4d56-a572-e11c4674106d
Levin, M.
3668029d-82f9-422c-8a69-42ccae2e88bf
Kwiatkowski, D.P.
a3f4e1b2-80d9-42ce-92f1-802669120bf8
Pollard, A.J.
53d9e953-ea8d-4d2c-b47d-82cf419615f8

Callaghan, M.J., Rockett, K., Banner, C., Haralambous, E., Betts, H., Faust, S., Maiden, M.C.J., Kroll, J. S., Levin, M., Kwiatkowski, D.P. and Pollard, A.J. (2008) Haplotypic diversity in human CEACAM genes: effects on susceptibility to meningococcal disease. Genes and Immunity, 9 (1), 30-37. (doi:10.1038/sj.gene.6364442). (PMID:17960155)

Record type: Article

Abstract

Adhesion between the opacity-associated adhesin (Opa) proteins of Neisseria meningitidis and human carcino-embryonic antigen cell adhesion molecule (CEACAM) proteins is an important stage in the pathogenesis of meningococcal disease, a globally important bacterial infection. Most disease is caused by a small number of meningococcal genotypes known as hyperinvasive lineages. As these are also carried asymptomatically, acquisition of them alone cannot explain why only some hosts develop meningococcal disease. Our aim was to determine whether genetic diversity in CEACAM is associated with susceptibility to meningococcal disease. Frequency distributions of alleles, genotypes and haplotypes were compared in four CEACAM genes in 384 case samples and 190 controls. Linkage disequilibrium among polymorphic sites, haplotype structures and relationships were also analysed. A number of polymorphisms were observed in CEACAM genes but the diversity of CEACAM1, to which most Opa proteins bind, was lower, and a small number of high-frequency haplotypes were detected. Dose-dependent associations of three CEACAM haplotypes with meningococcal disease were observed, with the effect of carrying these haplotypes amplified in homozygous individuals. Two haplotypes were protective while one haplotype in CEACAM6 was associated with a twofold increase in disease susceptibility. These data imply that human CEACAM may be one determinant of human susceptibility to meningococcal disease

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Published date: January 2008
Keywords: ceacam, snp, haplotype, meningococcal, susceptibility

Identifiers

Local EPrints ID: 70815
URI: https://eprints.soton.ac.uk/id/eprint/70815
ISSN: 1466-4879
PURE UUID: 8086f5a5-6d18-4a45-8f0b-dcfddc78c221
ORCID for S. Faust: ORCID iD orcid.org/0000-0003-3410-7642

Catalogue record

Date deposited: 10 Mar 2010
Last modified: 20 Jul 2019 00:54

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Contributors

Author: M.J. Callaghan
Author: K. Rockett
Author: C. Banner
Author: E. Haralambous
Author: H. Betts
Author: S. Faust ORCID iD
Author: M.C.J. Maiden
Author: J. S. Kroll
Author: M. Levin
Author: D.P. Kwiatkowski
Author: A.J. Pollard

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