Expression of Vitamin D Receptor Associated Genes in the Aorta of Coronary Artery Disease Patients with and without Rheumatoid Arthritis

Ingvild Oma¹, Sverre Holm^2,3, Jacqueline Kirsti Andersen⁴, Ole K. Olstad⁵, Ida G. Fostad⁶, Torstein Lyberg⁵, Sven Martin Almdahl⁷, Øyvind Molberg⁸ and Ivana Hollan^9,10,11, ¹Innlandet Hospital Trust, Lillehammer, Norway, ²Research Institute for Internal Medicine, Oslo University Hospital, Rikshospitalet, Oslo, Norway, ³Lillehammer Hospital for Rheumatic Diseases, Lillehammer, Norway, ⁴Norwegian University of Science and Technology, Gjøvik, Norway, ⁵Department of Medical Biochemistry, Oslo University Hospital, Oslo, Norway, ⁶Department of Oral Biology, Faculty of Dentistry, University of Oslo, Oslo, Norway, ⁷Department of Cardiothoracic Surgery, University Hospital of North Norway, Tromsø, Norway, ⁸Oslo University Hospital, Oslo, Norway, ⁹Brigham and Women’s Hospital, Boston, MA, ¹⁰Harvard Medical School, Boston, MA, ¹¹Lillehammer Hospital for Rheumatic Diseases, Lillahammer, Norway

Meeting: 2016 ACR/ARHP Annual Meeting

Date of first publication: September 28, 2016

Keywords: Atherosclerosis, coronary artery disease and rheumatoid arthritis (RA), Gene Expression, Vitamin D

Session Information

Date: Monday, November 14, 2016

Title: Rheumatoid Arthritis – Clinical Aspects - Poster II: Co-morbidities and Complications

Session Type: ACR Poster Session B

Session Time: 9:00AM-11:00AM

Background/Purpose: Vitamin D has an important role in the immune system, and has been linked to inflammation, rheumatoid arthritis (RA) and coronary artery disease (CAD)[1, 2]. However, the exact mechanisms how vitamin D is involved in these processes are still unclear. Therefore, the aim of this study was to compare the expression of vitamin D receptor (VDR) associated genes in the aortic adventitia of CAD patients with and without RA.

Methods: RNA was isolated, and Affymetrix microarray was used to determine the gene expression profile in specimens from the ascending aorta in 8 patients with CAD and 8 patients with CAD and RA from the Feiring Heart Biopsy Study. Partek Genomics Suite software was used to identify differentially expressed genes by one-way ANOVA (p<0.05; FC>1.1), and differences in expression of VDR associated genes were determined by Ingenuity Pathway Analysis.

Results: Among the 15586 transcripts that were identified, pathway analysis determined two genes within the VDR signaling pathway, Growth arrest and DNA-damage-inducible protein 45 alpha (GADD45A) (p=0.006; FC=1.474) and Nuclear Receptor Corepressor 1 (NCOR1) (p=0.005; FC=1,210), that where both up-regulated in RA patients.

Conclusion: GADD45A induces cell cycle arrest, DNA repair and apoptosis in response to various environmental stresses [3], and NCOR1 has an important role as a gene-specific integrator of positive and negative signals that control inflammation [4]. In theory, the accelerated atherosclerosis in RA might be related to the up-regulation of GADD45A and NCOR1 through the VDR signaling pathway. 1. Urruticoechea-Arana, A., et al., Vitamin D deficiency in chronic inflammatory rheumatic diseases: results of the cardiovascular in rheumatology [CARMA] study. Arthritis Res Ther, 2015. 17: p. 211.

2. Norman, P.E. and J.T. Powell, Vitamin D and cardiovascular disease. Circ Res, 2014. 114(2): p. 379-93.

3. Rosemary Siafakas, A. and D.R. Richardson, Growth arrest and DNA damage-45 alpha (GADD45alpha). Int J Biochem Cell Biol, 2009. 41(5): p. 986-9.

4. Glass, C.K. and K. Saijo, Nuclear receptor transrepression pathways that regulate inflammation in macrophages and T cells. Nat Rev Immunol, 2010. 10(5): p. 365-76.

Disclosure: I. Oma, None; S. Holm, None; J. K. Andersen, None; O. K. Olstad, None; I. G. Fostad, None; T. Lyberg, None; S. M. Almdahl, None; Ø. Molberg, None; I. Hollan, South-Eastern Norway Regional Health Authority, 2,the Norwegian Society for Rheumatology, 2,the Norwegian Rheumatism Association of the Norwegian Women’s Public Health Association, 2.

To cite this abstract in AMA style:

Oma I, Holm S, Andersen JK, Olstad OK, Fostad IG, Lyberg T, Almdahl SM, Molberg Ø, Hollan I. Expression of Vitamin D Receptor Associated Genes in the Aorta of Coronary Artery Disease Patients with and without Rheumatoid Arthritis [abstract]. Arthritis Rheumatol. 2016; 68 (suppl 10). https://acrabstracts.org/abstract/expression-of-vitamin-d-receptor-associated-genes-in-the-aorta-of-coronary-artery-disease-patients-with-and-without-rheumatoid-arthritis/. Accessed .

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