THE GENETIC SUSCEPTIBILITY TO GRAVES-DISEASE

Graves' disease (GD) develops as a result of a complex interaction bet ween genetic susceptibility genes and likely environmental factors. Mo st epidemiological data support an important genetic contribution to t he development of GD. The concordance rate of GD in monozygotic twins is 30-60% and in dizygotic twins 3-9%, and thyroid autoantibodies have been reported in up to 50% of the siblings of patients with GD. For m any years now, HLA studies have consistently shown an increased freque ncy of HLA-DR3 in Caucasian patients with GD; bur with only a risk rat io of 3-5. However, recent advances in human genome mapping techniques have enabled the study of many other candidate genes. Of these additi onal, non-HLA genes, only CTLA-4 has been consistently found to be ass ociated with GD. Using a linkage based approach which only detects hig hly significant susceptibility genes we have recently reported prelimi nary results which demonstrated that a marker located similar to 25 cM from the TSH receptor gene on chromosome 14q31 is linked to GD and in the same vicinity as the IDDM-11 locus. Such results, if confirmed, m ay signal the presence of a gene family related to endocrine autoimmun ity on chromosome 14q31.