Association of intercellular adhesion molecule-1 gene with type 1 diabetes.
Nejentsev S., Guja C., McCormack R., Cooper J., Howson JMM., Nutland S., Rance H., Walker N., Undlien D., Ronningen KS., Tuomilehto-Wolf E., Tuomilehto J., Ionescu-Tirgoviste C., Gale EAM., Bingley PJ., Gillespie KM., Savage DA., Carson DJ., Patterson CC., Maxwell AP., Todd JA.
Intercellular adhesion molecule-1 (ICAM-1) functions via its ligands, the leucocyte integrins, in adhesion of immune cells to endothelial cells and in T cell activation. The third immunoglobulin-like extracellular domain binds integrin Mac-1 and contains a common non-conservative aminoacid polymorphism, G241R. Phenotypically, ICAM-1 has been associated with type 1 diabetes, a T-cell-mediated autoimmune disease. We assessed two independent datasets, and noted that R241 was associated with lower risk of type 1 diabetes than is G241 (3695 families, relative risk 0.91, p=0.03; 446 families, 0.60, p=0.006). Our data indicate an aetiological role for ICAM-1 in type 1 diabetes, which needs to be confirmed in future genetic and functional experiments.