Regression mapping of association between the human leukocyte antigen region and Graves' disease

Simmonds, Matthew J., Howson, Joanna M. M., Heward, Joanne M. , Cordell, Heather J., Foxall, Helen, Carr-Smith, Jackie, Gibson, Sarah M., Walker, Neil, Tomer, Yaron, Franklyn, Jayne A., Todd, John A. and Gough, Stephen C. L. (2005) Regression mapping of association between the human leukocyte antigen region and Graves' disease. American Journal of Human Genetics, 76 (1). pp. 157-163. ISSN 0002-9297

Full content URL:

2005 AJHG HLA DR DQ Regression Paper.pdf

Request a copy
[img] PDF
2005 AJHG HLA DR DQ Regression Paper.pdf - Whole Document
Restricted to Repository staff only

Item Type:Article
Item Status:Live Archive


The human leukocyte antigen class II genes DRB1, DQB1, and DQA1 are associated with Graves disease (GD), but, because of strong linkage disequilibrium within this region, the primary etiological variant(s) remains unknown. In the present study, 871 patients with GD and 621 control subjects were genotyped at the DRB1, DQB1, and DQA1 loci. All three loci were associated with GD (P = 1.45 x 10-12, P = 3.20 x 10-5, and P = 9.26 x 10-12, respectively). Stepwise logistic-regression analysis showed that the association could be explained by either DRB1 or DQA1 but not by DQB1. To extend previous results, the amino acid sequence of the exon 2-encoded peptide-binding domain of DRB1 was predicted for each subject, and, by use of logistic regression, each position was analyzed for association with GD. Of 102 amino acids, 70 were uninformative; of the remaining 32 amino acids, 13 were associated with GD (P values ranged from 2.20x10-4 to 1.2x10-12). The strongest association was at position B74. This analysis is consistent with the possibility that position B74 of exon 2 of the DRB1 molecule may have a specific and central role in autoantigen presentation by DRB1 to T lymphocytes. However, we cannot yet exclude a primary role for DQA1 or for other polymorphisms that affect DRB1 function or expression.

Keywords:HLA antigen class 2, HLA DQA1 antigen, HLA DQB1 antigen, HLA DR antigen, amino acid sequence, antigen presentation, article, binding site, case control study, controlled study, gene linkage disequilibrium, gene mapping, genetic polymorphism, genotype, Graves disease, human, logistic regression analysis, major clinical study, priority journal, T lymphocyte, Case-Control Studies, Chromosome Mapping, Genes, MHC Class II, Histocompatibility Antigens Class II, HLA-DQ Antigens, HLA-DR Antigens, Humans, Odds Ratio, Polymorphism, Genetic, Regression Analysis
Subjects:C Biological Sciences > C420 Human Genetics
Divisions:College of Science > School of Life Sciences
Related URLs:
ID Code:22633
Deposited On:01 Apr 2016 08:25

Repository Staff Only: item control page