Diabetes, Vol 46, Issue 11 1888-1892, Copyright © 1997 by American Diabetes Association

ARTICLES

The effect of HLA-B allele on the IDDM risk defined by DRB1*04 subtypes and DQB1*0302

S Nejentsev, H Reijonen, B Adojaan, L Kovalchuk, A Sochnevs, EI Schwartz, HK Akerblom and J Ilonen
Turku Immunology Centre and Department of Virology, University of Turku, Finland.

The genes encoding the HLA-DQ heterodimer molecules, DQB1 and DQA1, have been found to have the strongest association with IDDM risk, although there is cumulative evidence for the effect of other gene loci within the major histocompatibility complex gene region. After the HLA-DQ locus, the HLA-DR locus has been suggested most often as contributing to the disease susceptibility. In this study we analyzed at the population level the effect of DR4 subtypes and class I, HLA-B alleles, on IDDM risk when the influence of the DQ locus was stratified. In all three populations studied (Estonian, Latvian, and Russian), DQB1*0302 haplotypes most frequently carried DRB1*0401 or DRB1*0404. DRB1*0401 was the most prevalent subtype in IDDM patients, whereas DRB1*0404 was decreased in frequency. DRB1*0402 was also prevalent among Russian haplotypes, but was not associated with IDDM risk. When HLA-B alleles were analyzed, strong associations between the presence of specific B alleles and DRB1*04 subtypes were detected. The HLA-B39 allele was found significantly more often in DRB1*0404-DQB1*0302-positive patients than in healthy control subjects positive for this haplotype: 27 of 54 (50%) vs. 4 of 49 (8.2%) (P < 0.0001). The results demonstrate that DQ and DR genes cannot explain all of the HLA-linked susceptibility to IDDM, and that the existence of a susceptibility locus telomeric to DR is probable.
CiteULike    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				D. V. Serreze, T. M. Holl, M. P. Marron, R. T. Graser, E. A. Johnson, C. Choisy-Rossi, R. M. Slattery, S. M. Lieberman, and T. P. DiLorenzo MHC Class II Molecules Play a Role in the Selection of Autoreactive Class I-Restricted CD8 T Cells That Are Essential Contributors to Type 1 Diabetes Development in Nonobese Diabetic Mice J. Immunol., January 15, 2004; 172(2): 871 - 879. [Abstract] [Full Text] [PDF]

				M A Kelly, M L Rayner, C H Mijovic, and A H Barnett Molecular aspects of type 1 diabetes Mol. Pathol., February 1, 2003; 56(1): 1 - 10. [Abstract] [Full Text] [PDF]

				M. P. Marron, R. T. Graser, H. D. Chapman, and D. V. Serreze Functional evidence for the mediation of diabetogenic T cell responses by HLA-A2.1 MHC class I molecules through transgenic expression in NOD mice PNAS, October 15, 2002; 99(21): 13753 - 13758. [Abstract] [Full Text] [PDF]

				R. T. Graser, T. P. DiLorenzo, F. Wang, G. J. Christianson, H. D. Chapman, D. C. Roopenian, S. G. Nathenson, and D. V. Serreze Identification of a CD8 T Cell That Can Independently Mediate Autoimmune Diabetes Development in the Complete Absence of CD4 T Cell Helper Functions J. Immunol., April 1, 2000; 164(7): 3913 - 3918. [Abstract] [Full Text] [PDF]

				H. Donner, R. R. Tönjes, B. Van der Auwera, T. Siegmund, J. Braun, I. Weets, J. Herwig, R. Kurth, K. H. Usadel, and K. Badenhoop The Presence or Absence of a Retroviral Long Terminal Repeat Influences the Genetic Risk for Type 1 Diabetes Conferred by Human Leukocyte Antigen DQ Haplotypes J. Clin. Endocrinol. Metab., April 1, 1999; 84(4): 1404 - 1408. [Abstract] [Full Text]

				T. P. DiLorenzo, R. T. Graser, T. Ono, G. J. Christianson, H. D. Chapman, D. C. Roopenian, S. G. Nathenson, and D. V. Serreze Major histocompatibility complex class I-restricted T cells are required for all but the end stages of diabetes development in nonobese diabetic mice and use a prevalent T cell receptor alpha  chain gene rearrangement PNAS, October 13, 1998; 95(21): 12538 - 12543. [Abstract] [Full Text] [PDF]