title: Intercellular adhesion molecule-1: a protective haplotype against multiple sclerosis.
abstract: Intercellular adhesion molecule-1 (ICAM-1) and its receptors are adhesion molecules that play a key role in the transmigration of inflammatory cells through the blood-brain barrier, one of the earliest events in multiple sclerosis (MS), which leads to demyelination in the central nervous system. To investigate the role of genes encoding ICAM-1 and its receptors, we used a strategy of genetic linkage and association in 439 case-parent MS families of French origin, well characterized according to HLA status and severity. We demonstrate that the genes encoding ICAM-1 receptors do not influence MS susceptibility or severity. ICAM-1 had a modest, but significant effect on MS genetic susceptibility, independent of HLA and disease severity. We observed a rare, and an as yet unreported, ICAM-1 gene haplotype defined by amino acids K469 and R241 that was never transmitted to patients suggesting a protective effect against MS in our population.
authors.affiliation: Laboratoire des affections de la myéline et des canaux ioniques musculaires-INSERM U546, Faculté de Médecine Pitié-Salpêtrière, Paris, France.
authors.forename: I
authors.initials: I
authors.lastname: Cournu-Rebeix
authors.forename: E
authors.initials: E
authors.lastname: Génin
authors.forename: G
authors.initials: G
authors.lastname: Lesca
authors.forename: A
authors.initials: A
authors.lastname: Azoulay-Cayla
authors.forename: N
authors.initials: N
authors.lastname: Tubridy
authors.forename: E
authors.initials: E
authors.lastname: Noé
authors.forename: M
authors.initials: M
authors.lastname: Clanet
authors.forename: G
authors.initials: G
authors.lastname: Edan
authors.forename: F
authors.initials: F
authors.lastname: Clerget-Darpoux
authors.forename: G
authors.initials: G
authors.lastname: Sémana
authors.forename: B
authors.initials: B
authors.lastname: Fontaine
mesh_terms: D017668:Age of Onset; D000483:Alleles; D005260:Female; D005602:France / Q000453:epidemiology; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006684:HLA-DR Antigens / Q000235:genetics / Q000276:immunology; D006239:Haplotypes; D006579:Heterozygote; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics*; D008297:Male; D018895:Microsatellite Repeats; D009103:Multiple Sclerosis / Q000235:genetics*; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide
chemical_list: D006684:HLA-DR Antigens; D018799:Intercellular Adhesion Molecule-1