Influence of the TSH Receptor Gene on Susceptibility to Graves' Disease and Graves' Ophthalmopathy

Yin, Xiao‐Ming; Latif, Rauf; Bahn, Rebecca S.; Tomer, Yaron; Davies, Terry F.

doi:10.1089/thy.2008.0098

Cited by 54 publications

(44 citation statements)

References 44 publications

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“…The argument over whether GO is a disorder distinct from GD and simply inherited at the same time appears less impressive now that the TSHR has been identified as an important antigen and that titers of TSHR antibodies correlate with the disease (40,41). In the present study and in our previous observations (23), TSHR gene polymorphisms were no more prevalent in the population of patients with GD and GO compared to patients without GO. Nevertheless, the thought has persisted that particular susceptibility must bias a patient toward the development of the eye phenotype rather than such patients simply having a worse form of the same disorder.…”

Section: Discussioncontrasting

confidence: 51%

“…However, the distinct factors predisposing GD patients to the development of GO remain unclear (27). While claims for preferential genetic associations with GO (19,28) have been made, our own data have not substantiated such reports (23,27).…”

Section: Introductionmentioning

confidence: 62%

“…The susceptibility genes have been identified both by the candidate gene approach and by whole genome linkage and association studies (36). The identified genes have, to date, each provided only a small contribution to genetic susceptibility, including the TSHR gene (22,23), indicating that many genes must be involved. However, the concept of major, or necessary, gene polymorphisms that have to be inherited to develop the disease does not appear to apply to GD (37,38).…”

Section: Discussionmentioning

confidence: 99%

“…The protocol was the same as described in the previous study (23). Human genomic DNA (*25 ng) was amplified by PCR and 415-bp products were generated.…”

Section: Genotypingmentioning

confidence: 99%

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Genetic Profiling in Graves' Disease: Further Evidence for Lack of a Distinct Genetic Contribution to Graves' Ophthalmopathy

Yin

Latif

Bahn

et al. 2012

Thyroid

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Background: Graves' disease (GD), including Graves' ophthalmopathy or orbitopathy (GO), is an autoimmune disease with an environmental and genetic component to its etiology. The genetic contribution to the GO clinical phenotype remains unclear. Previous data from our laboratory and others have suggested that GO has no specific genetic component distinct from GD itself, while other reports have occasionally appeared suggesting that polymorphisms in genes such as CTLA4 and IL23R specifically increase the risk for GO. One of the criticisms of all these reports has been the clinical definition of the GO phenotype as distinct from hyperthyroid GD devoid of clinically significant eye involvement. The objective of this study was to take advantage of a phenotypically pure group of GD patients with GO and examine a series of genes associated with GD to determine if any were more definitively associated with GO rather than Graves' thyroid disease itself. Methods: To further examine whether specific susceptibility genes are associated with GO, we have performed further genetic association studies using highly characterized GO patients, many of whom had undergone orbital decompression surgery for their exophthalmos. We genotyped HLA, CTLA4, IL23R, and TSHR genes in a group of 256 Caucasian patients with severe GO (n = 199) and less severe GO (n = 57), and 90 patients with GD but no clinically apparent GO. Results: We found that the allele and genotype frequencies were not statistically different between GO and non-GO patients for any of the genes and gene combinations assessed. Conclusions: These results provide further evidence that patients with GO do not have a distinct genetic susceptibility to their eye disease and again suggest that environmental and/or epigenetic influences are at play.

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Section: Discussioncontrasting

confidence: 51%

Section: Introductionmentioning

confidence: 62%

Section: Discussionmentioning

confidence: 99%

“…The protocol was the same as described in the previous study (23). Human genomic DNA (*25 ng) was amplified by PCR and 415-bp products were generated.…”

Section: Genotypingmentioning

confidence: 99%

See 2 more Smart Citations

Genetic Profiling in Graves' Disease: Further Evidence for Lack of a Distinct Genetic Contribution to Graves' Ophthalmopathy

Yin

Latif

Bahn

et al. 2012

Thyroid

Self Cite

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“…Linkage and association of the CTLA-4 exon 1 polymorphism with GD, and to lesser extent with HT, has been found in several populations, although there seems to be some inconsistency, probably due to population heterogeneity [11,17,27,[30][31][32][33] (Table 1).…”

Section: Autoimmune Thyroid Diseasesmentioning

confidence: 99%

The soluble CTLA-4 receptor and its role in autoimmune diseases: an update

Saverino

Simone

Bagnasco

et al. 2010

Autoimmun Highlights

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CTLA-4, initially described as a membranebound molecule, is a costimulatory receptor transducing a potent inhibitory signal. Increasing evidence shows the CTLA-4 gene to be an important susceptibility locus for autoimmune endocrinopathies and other autoimmune disorders. A soluble form of cytotoxic T-lymphocyte-associated antigen-4 (sCTLA-4) has been established and shown to possess CD80/CD86 binding activity and in vitro immunoregulatory functions. sCTLA-4 is generated by alternatively spliced mRNA. Whereas low levels of sCTLA-4 are detected in normal human serum, increased serum levels are observed in several autoimmune diseases (e.g. Graves’ disease, myasthenia gravis, systemic lupus erythematosus, type 1 diabetes, systemic sclerosis, coeliac disease, autoimmune pancreatitis and primary biliary cirrhosis). The biological significance of increased sCTLA-4 serum levels is not fully clarified yet. On the one hand, it can be envisaged that sCTLA-4 specifically inhibits early T-cell activation by blocking the interaction of CD80/CD86 with the costimulatory receptor CD28. On the other hand, higher levels of sCTLA-4 could compete for the binding of the membrane form of CTLA-4 with CD80/CD86 in the later phases of T-lymphocyte activation, causing a reduction in inhibitory signalling. This double-edged nature of sCTLA-4 to block the binding of CD28 to CD80/CD86 may result in different outcomes during the clinical course of an autoimmune disease.

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Radioiodine Therapy of Hyperthyroidism in Graves’ Disease

Wong

Goh

2012

Therapeutic Nuclear Medicine

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Influence of the TSH Receptor Gene on Susceptibility to Graves' Disease and Graves' Ophthalmopathy

Cited by 54 publications

References 44 publications

Genetic Profiling in Graves' Disease: Further Evidence for Lack of a Distinct Genetic Contribution to Graves' Ophthalmopathy

Genetic Profiling in Graves' Disease: Further Evidence for Lack of a Distinct Genetic Contribution to Graves' Ophthalmopathy

The soluble CTLA-4 receptor and its role in autoimmune diseases: an update

Radioiodine Therapy of Hyperthyroidism in Graves’ Disease

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