Gene expression in Graves' ophthalmopathy and arm lymphedema: similarities and differences

Thyroid. 2011 Jun;21(6):663-74. doi: 10.1089/thy.2010.0217. Epub 2011 Apr 21.


Background: Graves' ophthalmopathy (GO) and lymphedema share some pathogenetic mechanisms, such as edema, inflammation, and adipogenesis. The aim of this study was to examine similarities and differences between chronic GO and chronic lymphedema.

Methods: Intraorbital adipose tissue was collected from patients with active (n = 10) or chronic GO (n = 10) and thyroid-healthy controls (n = 10). Arm subcutaneous adipose tissue was obtained from patients with chronic arm lymphedema (n = 10), where the unaffected arm served as a control. Gene expression was studied using microarray and real-time polymerase chain reaction.

Results: The following genes were significantly upregulated (p < 0.05) in lymphedema but not in GO and have functions in wound healing, fibrosis, fat metabolism, inflammation, differentiation, development, adhesion, and the cytoskeleton: ATP-binding cassette, sub-family G (WHITE), member 1 (ABCG1), actin, alpha 2, smooth muscle, aorta (ACTA2), secreted frizzled-related protein 2 (SFRP2), tenascin C (TNC), pentraxin-related gene, rapidly induced by IL-1 beta (PTX3), and carboxypeptidase X (M14 family), member 1 (CPMX1). In chronic GO, but not in lymphedema, adipocyte-related immediate early genes known to be overexpressed in patients with active GO were upregulated but at a lower level than previously shown for the active phase. Genes of the Wnt pathway, such as secreted frizzled-related protein 1, 2, and 3, were up- and downregulated in both chronic GO and lymphedema. Parathyroid hormone-like hormone (PTHLH) was downregulated (p = 0.01) and apolipoprotein L domain containing 1 (APOLD1) was upregulated (p = 0.05) in both active and chronic GO.

Conclusions: There are more differences than similarities between chronic ophthalmopathy and chronic lymphedema, but both conditions exhibit less inflammation and adipogenesis compared to the active phases. In lymphedema, fibrosis dominates. PTHLH, which can inhibit adipogenesis, is downregulated both in active and chronic ophthalmopathy, indicating the possibility of an increased risk of adipogenesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipogenesis / physiology*
  • Adipose Tissue / metabolism
  • Adult
  • Arm / pathology
  • Breast Neoplasms / complications
  • Down-Regulation
  • Female
  • Gene Expression
  • Gene Expression Profiling*
  • Graves Ophthalmopathy / metabolism*
  • Humans
  • Lymphedema / etiology
  • Lymphedema / metabolism*
  • Male
  • Microarray Analysis
  • Middle Aged
  • Parathyroid Hormone-Related Protein / biosynthesis
  • Up-Regulation


  • PTHLH protein, human
  • Parathyroid Hormone-Related Protein