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Association of intercellular adhesion molecule-1 gene with type 1 diabetes
Authors:Nejentsev Sergey  Guja Cristian  McCormack Rose  Cooper Jason  Howson Joanna M M  Nutland Sarah  Rance Helen  Walker Neil  Undlien Dag  Ronningen Kjersti S  Tuomilehto-Wolf Eva  Tuomilehto Jaakko  Ionescu-Tirgoviste Constantin  Gale Edwin A M  Bingley Polly J  Gillespie Kathleen M  Savage David A  Carson Dennis J  Patterson Chris C  Maxwell A Peter  Todd John A
Affiliation:Juvenile Diabetes Research Foundation/Wellcome Trust Diabetes and Inflammation Laboratory, Cambridge Institute for Medical Research, University of Cambridge, Addenbrooke's Hospital, CB2 2XY, Cambridge, UK. sergey.nejentsev@cimr.cam.ac.uk
Abstract: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.
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