Diabetic Perspectives

Rev Diabet Stud, 2005, 2(2):97-109 DOI 10.1900/RDS.2005.2.97

The Role of HLA Class I Gene Variation in Autoimmune Diabetes

Charles Sia1, 2

1Department of Immunology, United Biomedical Inc., 25 Davids Drive, Hauppage, New York 11788, USA.
2Department of Economics, University of Dortmund, 44227 Dortmund, Germany.
Address correspondence to: Charles Sia, e-mail: csia@unitedbiomedical.com

Keywords: type 1 diabetes, HLA class I, cross-study analysis, serotype association


The use of DNA-based genetic typing has enabled the identification of type 1 diabetes mellitus (T1DM) susceptible and protective major histocompatibility complex (MHC) class II alleles and haplotypes. The application of this approach has also progressed to locate MHC class I alleles that contribute to the clinicopathology of T1DM. Recent studies have shown a widespread involvement of genes from the MHC class I gene region in the clinicopathology of T1DM. These genes are shown to be involved in contributing to progression from the preclinical stage of the disease, which is characterized by the occurrence of islet-specific antibodies, to clinical disease and also to the occurrence of autoimmunity. They can either contribute directly to disease development or indirectly in concert with other susceptible MHC class II alleles or haplotypes via linkage disequilibrium. Class I alleles may also be negatively associated with T1DM. These findings are useful for the development of future strategies in designing tolerogenic approaches for the prevention or even reversal of T1DM. In this article, the latest evidence for the different kinds of participation of HLA class I genes in the etiology of T1DM is reviewed. A meta-analysis which included existing association studies was also carried out in order to re-assess the relevance of class I genes in diabetes development. The analysis of an enlarged heterogeneous sample confirmed the involvement of previously detected serotypes in the etiology of T1DM, such as A24, B8 and B18, and revealed hitherto unknown associations with B60 and B62. The analysis points out that much of the conflicting results of previous association studies originate from inadequate sample sizes and accentuate the value of future investigations of larger samples for identifying linkage in multigenic diseases.

Fulltext: HTML , PDF (277KB)

This article has been cited by other articles:

Dominant suppression of Addison’s disease associated with HLA-B15

Baker PR, Baschal EE, Fain PR, Nanduri P, Triolo TM, Siebert JC, Armstrong TK, Babu SR, Rewers MJ, Gottlieb PA, Barker JM, Eisenbarth GS

J Clin Endocrinol Metab 2011. 96(7):2154-2162

Genetic deficiency of Itgb2 or ItgaL prevents autoimmune diabetes through distinctly different mechanisms in NOD/LtJ mice

Glawe JD, Patrick DR, Huang M, Sharp CD, Barlow SC, Kevil CG

Diabetes 2009. 58(6):1292-1301

HLA and infectious diseases

Blackwell JM, Jamieson SE, Burgner D

Clin Microbiol Rev 2009. 22(2):370-385

Genome-wide association studies: progress and potential for drug discovery and development

Kingsmore SF, Lindquist IE, Mudge J, Gessler DD, Beavis WD

Nat Rev Drug Discov 2008. 7(3):221-230

Islet cell autoantibodies in African patients with Type 1 and Type 2 diabetes in Dar es Salaam Tanzania: a cross sectional study

Lutale J, Thordarson H, Holm P, Eide G, Vetvik K

J Autoimmune Dis 2007. 4:4