Endocrine Abstracts

Genome wide association screening (GWAS) has proved invaluable in determining otherwise undetected genetic effects for several common endocrine diseases. The largest GWAS performed in Graves’ disease (GD), to date, has not only confirmed association of several known gene regions, including the HLA region, TSHR and FCRL3, but has also identified several other possible regions of association with GD. As GD shares several susceptibility loci with other endocrin...

In addition to the HLA gene region, two further genes involved in the inhibition of T cell signalling, CTLA-4 and PTPN22, have been consistently associated with autoimmune disease (AID), highlighting the important role played by molecules in this pathway in AID susceptibility. The Programmed Cell Death 1 gene (PDCD1) on chromosome 2q37.3 encodes PD-1 which is involved in providing a negative signal to activated T cells. Large case-control studies have show...

Protein tyrosine phosphatases (PTPs) such as PTPN22, that encodes lymphoid tyrosine phosphatase (LYP), are important regulators of cell signalling. LYP, through interaction with various accessory molecules including Grb2 and Csk kinase, has been shown to be particularly important in regulating signal transduction from the T cell receptor. The identification of PTPN22 as a susceptibility locus for Graves’ disease (GD) led us to hypothesise that other PTPs may...

Graves’ disease (GD) and Hashimotos’ thyroiditis (HT), two of the most common autoimmune thyroid diseases (AITD), are caused by both shared and disease specific genetic determinants. In females one copy of the X chromosome is randomly inactivated, and although inactivation should occur with a parent of origin ratio of 50:50, skewed X chromosome inactivation (XCI) can occur, whereby >80% of a specific copy of the X chromosome is inactivated. Increased skewed XCI i...

Graves’ disease (GD) affects >2% of the population and occurs more frequently in females than males. Several hypotheses have been put forward to explain the female preponderance including increased immune responsiveness, gonadal steriods, sex chromosome susceptibility loci and, more recently, skewed X inactivation (XCI). XCI occurs in females causing one of their X chromosomes to be randomly inactivated enabling dosage compensation with males who only have one copy of...