Genotype-phenotype correlations in Graves' disease

Abstract

Graves' disease (GD) is a heterogeneous autoimmune disease affecting with varying degrees of severity the thyroid gland, orbital tissues and skin. The pathogenesis of GD involves a complex interplay between multiple genetic, environmental and endogenous factors. Although the genetic predisposition to GD is well established, the significance of genotype-phenotype correlations and the role of epigenetic modifications in the disease pathogenesis remains largely unknown. In this review, we provide an up-to-date overview of genotype-phenotype correlations and summarize possible clinical implications of genetic and epigenetic markers in GD patients. We will specifically discuss the association of genetic markers and epigenetic modifications with age of GD onset, severity of Graves' hyperthyroidism and the development of clinically evident Graves' orbitopathy.

Keywords: Graves’ disease; HLA antigen; autoimmunity; genotype-phenotype correlation; hyperthyroidism; orbitopathy; polymorphism.