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.

Original publication

DOI

10.1038/sj.gene.6364442

Type

Journal article

Journal

Genes and immunity

Publication Date

01/2008

Volume

9

Pages

30 - 37

Addresses

Department of Paediatrics, Centre for Clinical Vaccinology and Tropical Medicine, University of Oxford, Churchill Hospital, Headington, Oxford, Oxon, UK. martin.callaghan@paediatrics.ox.ac.uk

Keywords

Humans, Neisseria meningitidis, Meningococcal Infections, Genetic Predisposition to Disease, Adhesins, Bacterial, Carcinoembryonic Antigen, Antigens, Bacterial, Data Interpretation, Statistical, Case-Control Studies, Retrospective Studies, Cohort Studies, Gene Frequency, Haplotypes, Homozygote, Linkage Disequilibrium, Polymorphism, Single Nucleotide, Alleles, Genetic Variation