WHAT IS THE EVIDENCE OF GENETIC-FACTORS IN THE ETIOLOGY OF GRAVES-DISEASE - A BRIEF REVIEW

Graves' disease (GD) is generally thought of as a multifactorial disor der in which genetic susceptibility interacts with environmental and e ndogenous factors to cause disease. The importance of genetic factors is suggested by the clustering of GD within families and by a higher c oncordance rate for disease in monozygotic than in dizygotic twins. Th is has, however, recently been shown to be less pronounced than previo usly thought. During the last decade much effort has been put into cha racterization of the genetic background of GD. Until recently, most st udies have examined associations between GD and the human leukocyte an tigen (HLA) region, but recent advances in molecular techniques have o pened the way for whole genome screening. A number of HLA and non-HLA candidate genes have been proposed, but despite several large investig ations within multiplex families no major susceptibility genes have be en identified. This brief review discusses relevant articles published from 1940 through 1997 regarding the influence of genetic factors in the etiology of GD. Ongoing studies focus on whole genome screening in multiplex families as well as population-based twin studies. However, the possibility of GD being a heterogeneous disease without a single well-defined genotype and phenotype should be left open.