Genetic profiling in graves' disease: Further evidence for lack of a distinct genetic contribution to graves' ophthalmopathy

Xiaoming Yin, Rauf Latif, Rebecca Bahn, Terry F. Davies

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)730-736
Number of pages7
JournalThyroid
Volume22
Issue number7
DOIs
StatePublished - Jul 1 2012

Fingerprint

Graves Ophthalmopathy
Graves Disease
Genes
Phenotype
Exophthalmos
Eye Diseases
Thyroid Diseases
Genetic Association Studies
Hyperthyroidism
Genetic Predisposition to Disease
Decompression
Gene Frequency
Epigenomics
Autoimmune Diseases
Genotype

ASJC Scopus subject areas

  • Endocrinology
  • Endocrinology, Diabetes and Metabolism

Cite this

Genetic profiling in graves' disease : Further evidence for lack of a distinct genetic contribution to graves' ophthalmopathy. / Yin, Xiaoming; Latif, Rauf; Bahn, Rebecca; Davies, Terry F.

In: Thyroid, Vol. 22, No. 7, 01.07.2012, p. 730-736.

Research output: Contribution to journalArticle

Yin, Xiaoming ; Latif, Rauf ; Bahn, Rebecca ; Davies, Terry F. / Genetic profiling in graves' disease : Further evidence for lack of a distinct genetic contribution to graves' ophthalmopathy. In: Thyroid. 2012 ; Vol. 22, No. 7. pp. 730-736.
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