Endocrine Abstracts

Graves’ disease (GD) is a heterogeneous disorder affecting with varying degrees of severity the thyroid and eyes. This variety may suggest that complex interactions between genetic, environmental and endogenous factors influence the clinical course of GD. Although the genetic predisposition to GD is well established, the significance of genotype-phenotype correlations remains controversial. Moreover, the lack of complete phenotypic concordance in twin studies suggested that environmental and/endogenous factors are of great importance. The major environmental factor influencing the clinical course of GD is cigarette smoking.

Most evidence for genotype-phenotype correlations in GD is based now on case-control association studies with candidate genes. The following loci have been proposed to influence susceptibility to orbitopathy, age of onset of GD and/or severity of hyperthyroidism: HLA, PTPN22, CTLA4, CD40, TSHR, TG, TNF, ICAM-1, IFN-γ, IL-23R, NFKB1. Unfortunately the results of these studies have to be judged very carefully. The vast majority of studies are small and underpowered; replication studies are lacking or were unable to confirm the initial finding; the studied groups were often not characterized in detail. At present, while some genetic differences between subgroups of GD patients have been identified, none of the polymorphisms justifies genetic testing to guide therapy or preventive strategies. Genotype-phenotype correlations in GD remain to be elucidated in future, well designed and appropriately powered studies.

Declaration of interest: The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project.

Funding: This work was supported, however funding details are unavailable.