Abstract:
:Numerous studies have associated carriage of HLA-DRB1*1501, DQA1*0102 and DQB1*0602 (DR15, DQ6) with dominant resistance to type 1 diabetes and have concluded that one or more of the component HLA class II molecules mediate this effect. Mechanisms for MHC class II-mediated resistance to diabetes have been proposed from studies of transgenic mice, usually using the diabetes-prone non-obese diabetic (NOD) strain. However, these studies have not reached any consensus on a plausible mechanism. In this study we question why the role of central MHC genes in resistance to diabetes has not been addressed, as the central MHC carries markers of susceptibility to diabetes in linkage disequilibrium with several genes with known or putative immunoregulatory functions. To illustrate the type of studies required to address this issue, we selected diabetes patients and control subjects for carriage of HLA-DR15 and the C allele at position +738 in the inhibitor of kappa B-like gene (IKBL). These alleles mark the 7.1 haplotype (HLA-A3, B7, IKBL738*C, DR15, DQ6). HLA-DR15 was the most effective marker of resistance, but an effect may be evident with IKBL738*C in a larger study. Moreover, carriage of the entire haplotype was particularly rare in patients. The best explanation for this is that the critical gene lies between IKBL and HLA-DRB1, and is more closely linked to HLA-DRB1. Candidate genes at the centromeric end of the central MHC are reviewed, highlighting the need for further study.
journal_name
Immunol Cell Bioljournal_title
Immunology and cell biologyauthors
Price P,Cheong KY,Boodhoo A,Witt CS,McCann V,Christiansen FT,Allcock RJdoi
10.1046/j.1440-1711.2001.01043.xsubject
Has Abstractpub_date
2001-12-01 00:00:00pages
602-6issue
6eissn
0818-9641issn
1440-1711pii
1043journal_volume
79pub_type
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