We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Genotype effects and epistasis in type 1 diabetes and HLA-DQ trans dimer associations with disease.
- Authors
Koeleman, B. P. C.; Lie, B. A.; Undlien, D. E.; Dudbridge, F.; Thorsby, E.; de Vries, R. R. P.; Cucca, F.; Roep, B. O.; Giphart, M. J.; Todd, J. A.
- Abstract
Alleles of HLA class II genes DQB1, DQA1, and DRB1 in the MHC region are major determinants of genetic predisposition to type 1 diabetes (T1D). Several alleles of each of these three loci are associated with susceptibility or protection from disease. In addition, relative risks for some DR-DQ genotypes are not simply the sum or product of the single haplotype relative risks. For example, the risk of the DRB1*03-DQB1*02/DRB1*0401-DQB1*0302 genotype is often found to be higher than for the individual DRB1*03-DQB1*02 and DRB1*0401-DQB1*0302 homozygous genotypes. It has been hypothesized that this synergy or epistasis occurs through formation of highly susceptible trans-encoded HLA-DQ(a1, ß1) heterodimers. Here, we evaluated this hypothesis by estimating the disease associations of the range of DR-DQ genotypes and their inferred dimers in a large collection of nuclear families. We determined whether the risk of haplotypes in DRB1*0401-DQB1*0302-positive genotypes relative to the DRB1*03-DQB1*02-positive genotypes is different from that of DRB1*01-DQB1*0501, which we used as a baseline reference. Several haplotypes showed a different risk compared to DRB1*01-DQB1*0501, which correlated with their ability to form certain trans-encoded DQ dimers. This result provides new evidence for the potential importance of trans-encoded HLA DQ molecules in the determination of HLA-associated risk in T1D.Genes and Immunity (2004) 5, 381-388. doi:10.1038/sj.gene.6364106 Published online 27 May 2004
- Subjects
EPISTASIS (Genetics); MOLECULES; IMMUNITY; DISEASES
- Publication
Genes & Immunity, 2004, Vol 5, Issue 5, p381
- ISSN
1466-4879
- Publication type
Article
- DOI
10.1038/sj.gene.6364106