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 dizygotic twins. This has, however, recently been shown to be less pronounced than previousl y thought. During the last decade, much effort has been put into chara cterization of the genetic background of GD. Until recently most studi es have examined associations between GD and the human leukocyte antig en (HLA) region, but recent advances in molecular techniques have open ed the way for whole-genome screening. A number of HLA and non-HLA can didate genes have been proposed, but despite several large investigati ons within multiplex families no major susceptibility genes have been identified. This brief review discusses relevant articles published fr om 1940 through 1997 regarding the influence of genetic factors in the etiology of GD. Ongoing studies will focus on whole genome screening in multiplex families as well as population based twin studies. Howeve r, the possibility of GD being a heterogeneous disease without a singl e well-defined genotype and phenotype should be left open.