Jackie Carr-Smith

Regression Mapping of Association between the Human Leukocyte Antigen Region and Graves Disease

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 2.20 x 10(-4) to 1.2 x 10(-12)). The strongest association was at position beta 74. This analysis is consistent with the possibility that position beta 74 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.

Clustering of autoimmune disease in parents of siblings from the Type 1 diabetes Warren repository.

Aims  Autoimmune disorders co‐exist in the same individuals and in families, implying a shared aetiology. The aim of this study was to compare the prevalence of the common autoimmune diseases in the parents of siblings from the Type 1 diabetes Warren repository with the general population.

A single nucleotide polymorphism in the CD40 gene on chromosome 20q (GD-2) provides no evidence for susceptibility to Graves’ disease in UK Caucasians

objective  A genome‐wide screen in Graves’ disease (GD) has shown linkage to chromosome 20q, designated GD‐2. The gene encoding CD40, which stimulates lymphocyte proliferation and differentiation, maps to this region, and a single nucleotide polymorphism (SNP) at position −1 of the Kozak sequence within the gene has been reported to be associated with GD. The aim of this study was to determine whether this SNP of the CD40 gene confers susceptibility to GD in UK Caucasians.