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.
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Acknowledgements
We thank patients, their families and physicians for their help and support. The French Multiple Sclerosis Genetics Group, Genethon, the CIC Pitié-Salpêtrière, INSERM and the French Ministry of Research (CRB) provided help for the DNA bank. This work was supported by ARSEP, INSERM and FRM (Action 2000).
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Cournu-Rebeix, I., Génin, E., Lesca, G. et al. Intercellular adhesion molecule-1: a protective haplotype against multiple sclerosis. Genes Immun 4, 518–523 (2003). https://doi.org/10.1038/sj.gene.6364009
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DOI: https://doi.org/10.1038/sj.gene.6364009
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