HLA-encoded genetic predisposition in IDDM: DR4 subtypes may be associated with different degrees of protection

Diabetes
D E UndlienE Thorsby

Abstract

Recent studies have shown that the risk conferred by the high-risk DQA1*03-DQB1*0302 (DQ8) haplotype is modified by the DRB1*04 allele that is also carried by this haplotype. However, many of these studies suffer from lack of sufficient numbers of DQ-matched control subjects, which are necessary because there is a strong linkage disequilibrium between genes in the HLA complex. In the present study, using a large material of IDDM patients and DQ-matched control subjects, we have addressed the contribution of DR4 subtypes to IDDM susceptibility. Our data, together with recent data from others, clearly demonstrate that some DR4-DQ8 haplotypes are associated with disease susceptibility, while others are associated with protection, depending on the DRB1*04 allele carried by the same haplotype. In particular, our data demonstrate that DRB1*0401 confers a higher risk than DRB1*0404. Based on combined available data on the genetic susceptibility encoded by various DR4-DQ8 haplotypes and the amino acid composition of the involved DRbeta*04 chains as well as the ligand motifs for these DR4 subtypes, we have developed a unifying hypothesis explaining the different risks associated with different DR4-DQ8 haplotypes. We suggest that disease...Continue Reading

Citations

Jan 21, 2009·Archives of Dermatology·Rebecca J BrownEdward W Cowen
Apr 8, 1999·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·J A Todd
Aug 21, 2013·Archivum Immunologiae Et Therapiae Experimentalis·Kjersti S Rønningen
Jan 1, 2004·Human Immunology·Uma KangaNarinder K Mehra
Feb 14, 2013·Transfusion and Apheresis Science : Official Journal of the World Apheresis Association : Official Journal of the European Society for Haemapheresis·Najiba Fekih MrissaNasreddine Gritli
Feb 13, 2001·Human Immunology·E ZanelliR R de Vries
Mar 28, 2002·Human Immunology·Alfred PenfornisUNKNOWN DiMe (Childhood Diabetes in Finland) Study Group
Mar 1, 1997·Human Immunology·E Thorsby
Feb 26, 2000·Human Immunology·G Saruhan-DireskeneliF Darendeliler
Jan 23, 1999·Current Opinion in Immunology·S L ParryG Sønderstrup
Aug 30, 2001·Trends in Immunology·D E Undlien, E Thorsby
Mar 16, 2004·Pediatric Diabetes·O CinekK S Ronningen
Jul 22, 1997·Proceedings of the National Academy of Sciences of the United States of America·S D PatelG Sonderstrup-McDevitt
May 9, 1998·Proceedings of the National Academy of Sciences of the United States of America·M CongiaG Sønderstrup
Aug 31, 2006·Diabetes Technology & Therapeutics·Paul DantonioW Harry Hannon
Feb 1, 2003·Molecular Pathology : MP·M A KellyA H Barnett
Apr 4, 2001·The Journal of Clinical Investigation·G Sønderstrup, H O McDevitt
Sep 2, 2003·Journal of Pediatric Endocrinology & Metabolism : JPEM·Z SumníkO Cinek
Sep 12, 2002·Pharmacogenomics·Jan W A Smit, Michaela Diamant
Apr 23, 2014·Clinical Reviews in Allergy & Immunology·Zhiguo XieZhiguang Zhou
Nov 27, 2009·International Journal of Epidemiology·Elisabet WitsøKjersti S Rønningen
Aug 5, 1999·Autoimmunity·G FlandersM Rewers
Sep 24, 2004·Diabetes/metabolism Research and Reviews·Karin LarssonAke Lernmark
Jun 9, 2009·Best Practice & Research. Clinical Endocrinology & Metabolism·Eystein Husebye, Kristian Løvås
Mar 31, 2009·Endocrinology and Metabolism Clinics of North America·Eystein S Husebye, Kristian Løvås
Aug 15, 2015·Journal of Autoimmunity·Janelle A Noble
Dec 18, 2003·Annals of the New York Academy of Sciences·Amanda RewersHenry A Erlich

❮ Previous
Next ❯

Related Concepts

Related Feeds

American Diabetes Association Journals

Discover the latest diabetes research published by the journals from the American Diabetes Association.

Autoimmune Diabetes & Tolerance

Patients with type I diabetes lack insulin-producing beta cells due to the loss of immunological tolerance and autoimmune disease. Discover the latest research on targeting tolerance to prevent diabetes.