POLYMORPHISMS AND LINKAGE ANALYSIS FOR ICAM-1 AND THE SELECTIN GENE-CLUSTER

Genetic polymorphisms in leukocyte and endothelial cell adhesion molec ules may be important variables with regard to susceptibility to multi factorial disease processes that include an inflammatory component. Fo r this reason, polymorphisms were sought for intercellular adhesion mo lecule-1 (ICAM-1; gene symbol ICAM1) and for the three genes in the se lectin cluster, P-selectin, L-selectin, and E-selectin (gene symbols S ELF, SELL, and SELF, respectively). Two amino acid polymorphisms were identified for ICAM1; Gly or Arg at codon 241 and Lys or Glu at codon 469. Dinucleotide repeat polymorphisms were identified in the 3'-untra nslated region for ICAM-1 and in intron 9 for P-selectin. Restriction fragment length polymorphisms were found using cDNAs for each of the t hree selectin genes as probes; E-selectin with BglII, P-selectin with ScaI, and L-selectin with HincII. Linkage analysis was performed for t he selectin gene cluster and for ICAM-1 using the CEPH families; ICAM- 1 is very tightly linked to the LDL receptor on chromosome 19, and the selectin cluster is linked to markers at chromosome 1q23. (C) 1994 Ac ademic Press, Inc.