MULTIPLE-SCLEROSIS - THE INCREASED FREQUENCY OF THE ICAM-1 EXON-6 GENE POINT MUTATION GENETIC TYPE K469

Intracellular adhesion molecule-1 (ICAM-1) plays an important role in the cascade of adhesion events in the homing of inflammatory cells to the central nervous system (CNS) in experimental autoimmune encephalom yelitis (EAE) and in multiple sclerosis (MS). Two single-base ICAM-1 p olymorphisms have been described, in exons 4 and 6, changing codons 24 1 and 469 in the ICAM-1 gene, respectively. Both polymorphisms result in amino acid changes and can potentially lead to different interactio ns of ICAM-1 with its ligands. To detect ICAM-1 gene polymorphisms in MS, we have developed a highly sensitive and site-specific, two-stage, nested polymerase chain reaction. Genomic DNA was extracted from bloo d cells of 79 MS patients and 68 control subjects. The results were co nfirmed by direct dideoxy chain termination sequencing. The frequency of exon 6 allele T was found to be significantly higher in MS patients than in controls (68% vs 49%). Most interesting, the frequency of exo n 6 homozygote K469 was significantly higher in MS patients than in co ntrols (53% vs 34%). Higher frequency of the K469 genotype was found t o be independent of possible linkage with the previously described MS susceptibility factor, the HLA. class II DR2 allele. In the present st udy, we have shown for the first time the ICAM-1 gene polymorphisms in MS. The results indicate increased frequency of ICAM-1 exon 6 allele T in MS patients, which may contribute to the MS genetics background.