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.
%0 Journal Article
%1 callaghan_haplotypic_2008
%A Callaghan, M J
%A Rockett, K
%A Banner, C
%A Haralambous, E
%A Betts, H
%A Faust, S
%A Maiden, M C J
%A Kroll, J S
%A Levin, M
%A Kwiatkowski, D P
%A Pollard, A J
%D 2008
%J Genes and Immunity
%K Adhesins, Alleles, Antigen, Antigens, Bacterial, Carcinoembryonic Cohort Data Disease, Disequilibrium, Frequency, Gene Genetic Haplotypes, Homozygote, Humans, Infections, Interpretation, Linkage Meningococcal Neisseria Nucleotide, Polymorphism, Predisposition Retrospective Single Statistical, Studies Studies, Variation, meningitidis, to {Case-Control}
%N 1
%P 30--7
%R 10.1038/sj.gene.6364442
%T Haplotypic diversity in human CEACAM genes: effects on susceptibility to meningococcal disease
%U http://www.ncbi.nlm.nih.gov/pubmed/17960155
%V 9
%X 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.
@article{callaghan_haplotypic_2008,
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.},
added-at = {2011-03-11T10:05:34.000+0100},
author = {Callaghan, M J and Rockett, K and Banner, C and Haralambous, E and Betts, H and Faust, S and Maiden, M C J and Kroll, J S and Levin, M and Kwiatkowski, D P and Pollard, A J},
biburl = {https://www.bibsonomy.org/bibtex/28266d063a241ff96c2b6fc30b5cd54cd/jelias},
doi = {10.1038/sj.gene.6364442},
interhash = {bf2ee974aa28449b09a43b154e1069bb},
intrahash = {8266d063a241ff96c2b6fc30b5cd54cd},
issn = {1476-5470},
journal = {Genes and Immunity},
keywords = {Adhesins, Alleles, Antigen, Antigens, Bacterial, Carcinoembryonic Cohort Data Disease, Disequilibrium, Frequency, Gene Genetic Haplotypes, Homozygote, Humans, Infections, Interpretation, Linkage Meningococcal Neisseria Nucleotide, Polymorphism, Predisposition Retrospective Single Statistical, Studies Studies, Variation, meningitidis, to {Case-Control}},
month = jan,
note = {{PMID:} 17960155},
number = 1,
pages = {30--7},
shorttitle = {Haplotypic diversity in human {CEACAM} genes},
timestamp = {2011-03-11T10:05:38.000+0100},
title = {Haplotypic diversity in human {CEACAM} genes: effects on susceptibility to meningococcal disease},
url = {http://www.ncbi.nlm.nih.gov/pubmed/17960155},
volume = 9,
year = 2008
}