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This article is part of the supplement: 25th European Workshop for Rheumatology Research

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Genotype-dependent NOS-3 expression and rheumatoid arthritis

M Cattaruzza1, I Melchers2 and M Hecker1

Author Affiliations

1 Department of Cardiovascular Physiology, University of Göttingen, Germany

2 Clinical Research Unit for Rheumatology, University Medical Center, Freiburg, Germany

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Arthritis Research & Therapy 2005, 7(Suppl 1):P104  doi:10.1186/ar1625

The electronic version of this article is the complete one and can be found online at:

Received:11 January 2005
Published:17 February 2005

© 2005 BioMed Central Ltd

Poster presentation

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.


  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. PubMed Abstract | Publisher Full Text OpenURL

  2. Cattaruzza M, Sodowski W, Stojakovic M, Krzesz R, Hecker M: Interleukin-10 induction of nitric-oxide synthase expression attenuates CD40-mediated interleukin-12 synthesis in human endothelial cells.

    J Biol Chem 2003, 278:37874-37880. PubMed Abstract | Publisher Full Text OpenURL