Intercellular adhesion molecule-1: a protective haplotype against multiple sclerosis.
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.
Cournu-Rebeix
I
I
Laboratoire des affections de la myéline et des canaux ioniques musculaires-INSERM U546, Faculté de Médecine Pitié-Salpêtrière, Paris, France.
Génin
E
E
Lesca
G
G
Azoulay-Cayla
A
A
Tubridy
N
N
Noé
E
E
Clanet
M
M
Edan
G
G
Clerget-Darpoux
F
F
Sémana
G
G
Fontaine
B
B
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
D006684:HLA-DR Antigens; D018799:Intercellular Adhesion Molecule-1