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...

Recent genome wide screens performed by the Wellcome Trust Case Control Consortium using 500k single nucleotide polymorphisms (SNP) genotyping arrays have detected several novel susceptibility loci for the common autoimmune diseases (AIDs): Crohn’s disease (CD), type 1 diabetes (T1D) and rheumatoid arthritis (RA). PTPN2, which encodes TCPTP an important negative regulator of inflammation, is one such locus. The rs2542151 SNP in PTPN2 was shown to be highly a...

Autoimmune thyroid diseases (AITD), Graves’ disease (GD) and Hashimoto’s thyroiditis (HT) are common, but there is limited information on the prevalence of co-existing auto-immune diseases (AID). We prospectively collected 3309 patients with AITD and determined prevalences of other autoimmune diseases in index cases and relatives. Overall, 10.3% of 2806 GD patients and 18.1% of 503 HT subjects reported a co-existing AID. Rheumatoid arthritis was the commonest AID in ...

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...

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...