Volume 7 Supplement 1

25th European Workshop for Rheumatology Research

Open Access

Genotype-dependent NOS-3 expression and rheumatoid arthritis

  • M Cattaruzza1,
  • I Melchers2 and
  • M Hecker1
Arthritis Research & Therapy20057(Suppl 1):P104

DOI: 10.1186/ar1625

Received: 11 January 2005

Published: 17 February 2005

The -786C-variant of the endothelial nitric oxide synthase nos-3 gene has been shown to be associated with coronary artery disease because of a blunted inducibility of gene expression [1]. IL-10, a cytokine involved in TH1/TH2-cell differentiation, is a new stimulus for NOS-3 expression [2].

We here address the question whether IL-10-induced NOS-3 expression is decreased in individuals with the -786C/C genotype and, if so, whether a TH1-mediated disease like rheumatoid arthritis is associated with this genotype.

Endothelial cells were isolated from an umbilical cord vein of known genotype and cultured as described [1]. The expression of NOS-3 was analysed by real-time semi-quantitative RT-PCR [1]. Genotyping was performed as described elsewhere [1]. Patients met the revised criteria of the ACR for the classification of rheumatoid arthritis, and donated blood samples after informed consent.

Primary human umbilical vein endothelial cells with the -786C/C genotype did not respond with an increase in NOS-3 expression to IL-10 incubation (5 ng/ml). This defect could be repaired after pre-incubation of the cells with a decoy oligonucleotide (10 μmol/l) directed against the C-variant of the promoter. Among 587 patients with rheumatoid arthritis tested, incidences for the -786C/C genotype were significantly higher than in the general population (17% versus 11.7%; P < 0.01).

NOS-3 is one mediator of anti-inflammatory IL-10 actions. Individuals with the -786C/C nos-3-genotype have an increased risk for the development of rheumatoid arthritis. This might be due to the IL-10 insensitivity of the C-variant of the promoter.



Supported by a grant of the BMBF (competence network rheumatism) to IM.

Authors’ Affiliations

Department of Cardiovascular Physiology, University of Göttingen
Clinical Research Unit for Rheumatology, University Medical Center


  1. Cattaruzza M, Guzik TJ, Slodowsky W, Pelvan A, Becker J, Halle M, Buchwald AB, Channon KM, Hecker M: Shear stress insensitivity of endothelial nitric oxide synthase expression as a genetic risk factor for coronary heart disease. Circ Res. 2004, 95: 841-847. 10.1161/01.RES.0000145359.47708.2f.View ArticlePubMedGoogle Scholar
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© BioMed Central Ltd 2005