Association of intercellular adhesion molecule-1 gene with type 1 diabetes |
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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 |
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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 |
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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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