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Can MHC class II genes mediate resistance to type 1 diabetes?
P Price1, K Y Cheong, A Boodhoo
1Department of Pathology, University of Western Australia, Nedlands. pprice@cyllene.uwa.edu.au
Immunology and Cell Biology
|March 21, 2002
Summary
The HLA-DR15 gene variant strongly protects against type 1 diabetes. Researchers identified a critical gene linked to HLA-DR15, potentially located between IKBL and HLA-DRB1, offering new insights into diabetes resistance.
Area of Science:
- Immunogenetics
- Human Genetics
- Diabetes Research
Background:
- Numerous studies link HLA-DRB1*1501, DQA1*0102, and DQB1*0602 (DR15, DQ6) to dominant resistance against type 1 diabetes.
- Proposed mechanisms for MHC class II-mediated diabetes resistance, often studied in non-obese diabetic (NOD) mice, lack consensus.
Purpose of the Study:
- To investigate the role of central Major Histocompatibility Complex (MHC) genes in diabetes resistance.
- To explore the association of the 7.1 haplotype (HLA-A3, B7, IKBL738*C, DR15, DQ6) with type 1 diabetes susceptibility and resistance.
Main Methods:
- 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).
- Analyzed the 7.1 haplotype's prevalence in patients and controls.
Main Results:
- HLA-DR15 was the most potent marker for diabetes resistance.
- The 7.1 haplotype was notably rare in diabetes patients.
- An association between IKBL738*C and resistance may be observable in larger cohorts.
Conclusions:
- The critical gene conferring diabetes resistance is likely located between IKBL and HLA-DRB1, with closer linkage to HLA-DRB1.
- Further investigation into candidate genes at the centromeric end of the central MHC is warranted.