Searchable abstracts of presentations at key conferences in endocrinology

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...

ea0011p880 | Thyroid | ECE2006

Do SNPs within the PTPN22 gene contribute to autoimmune disease via different mechanisms?

Heward J , Simmonds M , Franklyn JA , Gough SC

Graves’ disease (GD) is an autoimmune disorder of the thyroid gland. Autoimmune diseases cluster within families and individuals, leading to the hypothesis of common autoimmunity genes being shared between diseases. This has been confirmed through studies demonstrating association of the HLA region, the CTLA-4 gene and the PTPN22 gene with many disorders including GD and rheumatoid arthritis (RA). We and others have confirmed highly significant association of the R620W SN...

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...

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...

ea0019p375 | Thyroid | SFEBES2009

Association of another member of the FCRL family with Graves' disease: further evidence for disrupted B cell signalling in disease pathogenesis

Simmonds M J , Newby P R , Franklyn J A , Gough S C L

Identifying the pathogenic pathways involved in complex diseases such as Graves’ disease (GD) has proved challenging. Although several genetic risk factors, including the HLA class II region, CTLA4, PTPN22 and CD25, encode molecules playing key roles in antigen presentation and controlling T cell recognition/signalling, the identification of novel susceptibility loci has the potential to provide further insights into disease pathogenesis. Recently gen...

ea0013p325 | Thyroid | SFEBES2007

Preliminary evidence for association of PTPN12 with Graves’ ophthalmopathy

Brand Oliver J , Syed Ateeq A , Franklyn Jayne A , Gough Stephen CL , Heward Joanne M , Simmonds Matthew J

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...

ea0007p240 | Thyroid | BES2004

Defining aetiological variants within the HLA class II region that lead to the development of Graves' disease

Simmonds M , Heward J , Howson J , Cordell H , Walker N , Todd J , Franklyn J , Gough S

Genetic variants of the HLA class II region (DRB1, DQB1 and DQA1) and CTLA-4 contribute to susceptibility to Graves' disease (GD). Whilst disease susceptibility has been mapped to a non-coding 6.1kb 3' region of CTLA-4, the primary aetiological variants within the HLA class II region remain unknown. The aims of this study were (i) determine which of the three HLA class II loci account for the primary association with GD and (ii) examine disea...

ea0003p155 | Genetics | BES2002

A nonsense mutation in exon two of the DNASE1 gene is not present in UK subjects with SLE and autoimmune thyroid disease

Simmonds M , Heward J , Allahabadia A , Foxall H , Gordon C , Franklyn J , Gough S

Systemic lupus erythematosus (SLE) is characterised by the activation of autoreactive T and B cells and the production of autoantibodies. Concordance rates in monozygotic and dizygotic twins, along with familial clustering, suggest that SLE has a strong genetic component. Moreover, the co-existence of SLE and other autoimmune diseases within individuals, including autoimmune thyroid disease (ATD), suggests a sharing of general autoimmune susceptibility loci. Case control studi...