The Association of HLA with Autoimmune Thyroid Disease in Newfoundland. The Influence of HLA Homozygosity in Graves’ Disease

Abstract

Patients (47) with Graves'' disease, 73 with thyroiditis and 128 controls drawn from the same geographical area of Newfoundland were HLA [histocompatability antigen] typed. The frequency of HLA-B8 was significantly increased in the Graves'' disease patients when compared to the control group giving a relative risk of 3.9. There were no significant HLA differences between the thyroiditis and control groups. Homozygosity for the HLA haplotype, which is common in this island population, was more common in Graves'' disease patients (12.8%) than in controls (5.5%) but did not reach statistical significance in this sample. Homozygosity was due in 5 of the 6 cases to either an A1;B8 haplotype or an A2;B8 haplotype. This contrasted with an apparently random assortment of haplotypes in the control and thyroiditis groups. Calculations suggest that homozygosity for a B8 haplotype confers an additional risk over heterozygosity for B8 of about 3.5-fold; homozygosity had no observable influence on the severity of the disease. B8, or an allele in linkage disequilibrium with it, may determine the susceptibility of an individual to developing Graves'' disease.