Searchable abstracts of presentations at key conferences in endocrinology

ea0007s28 | Molecular basis of thyroid disease | BES2004

Gene linkage and association studies in autoimmune thyroid disease

Gough S

Autoimmune thyroid disease (AITD) clusters in families pointing, at least in part, to a genetic basis for disease. Subjects with AITD and other family members also have an increased risk for the development of other autoimmune diseases such as type 1 diabetes (TID) and rheumatoid arthritis suggesting the involvement of general autoimmunity genes. In common with other autoimmune diseases the HLA region was the first cluster of genes to be reported to be associated with AITD. Mo...

ea0003p152 | Genetics | BES2002

No association of a 3' UTR polymorphism of the interleukin-12 P40 (IL12B) gene with Grave's disease in a UK population

Heward J , Allahabadia A , Franklyn J , Gough S

Graves' disease (GD) is an autoimmune disorder of the thyroid gland, of which the aetiology is unknown, but susceptibility to disease is thought to result from both genetic and environmental factors. Familial clustering data suggests that GD is a polygenic disorder, with laboratory studies identifying the HLA gene region and the CTLA-4 gene region as susceptibility loci. However, together the HLA region and the CTLA-4 gene regions only contribute about 50% towards the genetic ...

ea0019p372 | Thyroid | SFEBES2009

Confirmation of the chromosome 2q37 region as a susceptibility locus for Graves’ disease

Newby P , Pickles O , Franklyn J , Gough S , Simmonds M

Genome wide association (GWA) studies have revolutionised the search for new susceptibility loci for complex diseases such as Graves’ disease (GD), by confirming association of known genes and identifying several novel susceptibility loci. The high density lipoprotein binding protein (HDLBP) on chromosome 2q37 is one such novel locus recently identified by the WTCCC as part of a 14 500 nonsynonymous single nucleotide polymorphisms (SNP) screen performed in 900 UK C...

ea0010oc18 | Young Endocrinologist session | SFE2005

Functional SNPs involved in NF-κB signalling and binding pathways and their contribution to the pathogenesis of graves’ disease

Simmonds M , #Heward|# , #Carr-Smith|# , #Foxall|# , #Franklyn|# , Gough S

The HLA class II region, CTLA-4 and PTPN22, have been consistently associated with autoimmune disease (AID). Recently, three DNA variants, two of which (M55V and 001Msp) are present in NF-κB inhibitors SUMO-4 and MAP3K7IP2, and one of which (fcrl3_3) modulates NF-κB binding and production of the B cell surface molecule FCRL3, have been reported to be associated with a number of AIDs. The aim of this study was to investigate genetic variati...

ea0010p91 | Thyroid | SFE2005

Lack of association of interleukin-13 polymorphisms with Graves’ disease

Heward J , Simmonds M , Franklyn J , Gough S

Genome wide screens in Graves’ disease (GD) have identified several regions of linkage which may harbour genes which contribute to disease susceptibility. One such region, on chromosome 5q31-33, contains a cytokine cluster which includes interleukin-13 (IL-13). This molecule plays a key role in IgE production, which has been reported to be elevated in patients with GD. Two functional single nucleotide polymorphisms (SNPs), -1112 and +2044, within the IL-13 gene were recen...

ea0007oc22 | Thyroid | BES2004

Defining genetic predictors for the development of Graves' disease in young females

Collins J , Heward J , Cordell H , Franklyn J , Gough S

The HLA and CTLA-4 gene regions, on chromosomes 6p21 and 2q33 respectively, have been consistently associated with Graves' disease (GD). Recent data indicate that both DRB1 (in the HLA class II region) and the 3' untranslated region of the CTLA-4 gene are the most likely regions harbouring the aetiological variants for susceptibility to GD. It is not known, however, whether these variants lead to expression of specific sub-phenotypes in subjects with GD, or contribute to disea...

ea0007p227 | Thyroid | BES2004

No association of a polymorphism in the kozak sequence of the CD40 gene and Graves' disease in a UK Caucasian population

Foxall H , Heward J , Franklyn J , Gough S

Graves' disease (GD) is an autoimmune disease of the thyroid gland with unknown aetiology thought to be caused by a complex interaction between genetic and environmental factors. To date, the HLA region on chromosome 6p21 and the CTLA-4 gene on chromosome 2q33 are thought to account for about 50% of the genetic component of GD with the remaining genetic contribution likely to be made up of many genes each exerting a small effect on predisposition to disease. A recent study (To...

ea0005p264 | Thyroid | BES2003

Is the thyroglobulin gene a susceptibility locus for autoimmune thyroid disease in the UK?

Collins J , Heward J , Franklyn J , Gough S

The autoimmune thyroid diseases (AITDs), Graves' disease (GD) and Hashimoto's thyroiditis (HT), are thought to be caused by complex interactions between genetic and environmental factors, which result in an organ-specific autoimmune response being directed against the thyroid gland. GD and HT, although clinically distinct, share many immunological and histological features. Several potential susceptibility genes for AITD have been investigated, although to date only the HLA an...

ea0005p265 | Thyroid | BES2003

Assessment of UK caucasian allele frequencies of known TNF-alpha polymorphisms and their association with Graves' disease

Simmonds M , Nithiyananthan R , Heward J , Franklyn J , Gough S

Tumour necrosis factor-alpha (TNF-alpha) plays an important role in the initiation and regulation of the cytokine cascade during an inflammatory response and is, therefore, a good candidate for involvement in the development of autoimmune disease. The TNF-alpha gene has been mapped to chromosome 6p21.3 and many single nucleotide polymorphisms (SNPs) have been detected within the gene that could affect its function. The allele frequencies of these SNPs and their relationship to...

ea0019p373 | Thyroid | SFEBES2009

Further evidence for a key role of FcGR2a in autoimmunity

Yesmin K , Hargreaves C , Newby P , Brand O , Heward J , Franklyn J , Gough S , Simmonds M

Autoimmune diseases (AIDs) have been shown to share a series of genetic susceptibility loci, including the HLA class II region, CTLA-4 and PTPN22, indicating the sharing of key pathways between diseases. Recently, the rs1801274 single nucleotide polymorphism (SNP) within the Fc gamma receptor 2a gene (FcGR2a) has been shown to be associated with several common AIDs including type 1 diabetes, rheumatoid arthritis and coeliac disease. FcGR2a is an immune mod...