Address of Corresponding Author

Horm Res 2005;64:180-188 (DOI: 10.1159/000089190)

  Key Words

• Diabetes mellitus, type 1
• Human leukocyte antigens
• Protein tyrosine phosphatase
• Cytotoxic T-lymphocyte-associated antigen 4
• Minisatellite repeats, insulin

  Abstract

The T-cell mediated autoimmune process that destroys pancreatic cells in type 1 diabetes (T1D) is a complex phenotype influenced by multiple genetic and environmental factors. Human leukocyte antigen (HLA) accounts for about half of the genetic susceptibility, through a large variety of protective and predisposing haplotypes. Other important loci associated with T1D, with much smaller effects than HLA, include the insulin variable number of tandem repeats, PTPN22, and CTLA-4. Detecting the association and confirming it beyond doubt is only the first step. Identifying the functional variant from among a block of polymorphisms in tight linkage disequilibrium and determining its biological consequences can be an even more challenging task. It is hoped that the identification of additional loci and functional analysis of known ones, no matter how small each individual effect is, will provide: (1) pathophysiological insights necessary for the development of preventive interventions; (2) risk prediction to identify individuals that can benefit from them, and (3) potentially, identification of distinct subgenotypes, with different immune dysregulation pathways leading to the common disease phenotype that may respond to different preventive interventions.

Copyright © 2005 S. Karger AG, Basel

  Author Contacts

Constantin Polychronakos
Division of Pediatric Endocrinology, McGill University Health Center
2300 Tupper, Montreal, QC, H3H 1P3 (Canada)
Tel. +1 514 412 4315, Fax +1 514 412 4264
E-Mail constantin.polychronakos@mcgill.ca

  Article Information

Published online: October 24, 2005
Number of Print Pages : 9
Number of Figures : 4, Number of Tables : 1, Number of References : 59