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AB0030 The LP13.3 genomic region -RS599839- is associated with endothelial dysfunction in patients with rheumatoid arthritis
  1. R. Lόpez-Mejías1,
  2. C. González-Juanatey2,
  3. M. García-Bermúdez3,
  4. S. Castañeda4,
  5. J.A. Miranda-Filloy5,
  6. R. Blanco1,
  7. J. Llorca6,
  8. J. Martín7,
  9. M.A. González-Gay8
  1. 1Department of Rheumatology, Hospital Universitario Marqués de Valdecilla, Ifimav, Santander
  2. 2Cardiology Division, Hospital Xeral-Calde, Lugo
  3. 3Instituto de Parasitología y Biomedicina Lόpez-Neyra, Ipbln-Csic, Granada
  4. 4Rheumatology Department, Hospital Universitario la Princesa, IIS-Princesa, Madrid
  5. 5Division of Rheumatology, Hospital Xeral-Calde, Lugo
  6. 6Department of Epidemiology and Computational Biology, School of Medicine, University of Cantabria, and CIBER Epidemiología y Salud Pública (CIBERESP), Ifimav, Santander
  7. 7Instituto de Parasitología y Biomedicina Lόpez-Neyra, Ipbln-Csic, Granada
  8. 8Department of Rheumatology, Hospital Universitario Marqués de Valdecilla, Ifimav, Santander, Spain

Abstract

Background Rheumatoid arthritis (RA) is a complex polygenic autoimmune inflammatory disease with high risk of cardiovascular (CV) complications as consequence of accelerated atherosclerosis [1]. Recent studies have emphasized the relevance of several genetic polymorphisms in the susceptibility to CV disease in RA [2, 3]. Genome-wide association studies (GWAS) revealed that the polymorphism rs599839 (A>G) is associated with CAD [4]and with higher plasma total and LDL cholesterol levels [5].

Objectives Wwe aimed to determine, for first time, the potential role of rs599839 polymorphism in the development of endothelial dysfunction in a cohort of RA patients without clinically evident CV disease.

Methods 128 RA patients without history of CV events were genotyped for rs599839 A/G polymorphism. Presence of endothelial dysfunction was assessed by brachial ultrasonography (brachial flow-mediated endothelium-dependent [FMD]).

Results Patients carrying the allele G exhibited more severe endothelial dysfunction (FMD%: 4.61±3.94%) than those carrying the wild allele A (FMD%: 6.01±5.15%) (p=0.08). Adjustment for gender, age at the time of study, follow-up time and classic CV risk factors disclosed a significant association between the rs599839 polymorphism and FMD (G vs. A: p=0.0062).

Conclusions Our results confirm an association of the rs599839 polymorphism with endothelial dysfunction in RA.

This study was supported by two grants from “Fondo de Investigaciones Sanitarias” PI06-0024 and PI09/007/48 (Spain) and partially supported by RETICS Program, RD08/0075 (RIER) from ``Instituto de Salud Carlos III'' (ISCIII).

  1. Chung CP, Oeser A, Raggi P, Gebretsadik T, Shintani AK, Sokka T, Pincus T, Avalos I, Stein CM. Increased coronary-artery atherosclerosis in rheumatoid arthritis: relationship to disease duration and cardiovascular risk factors. Arthritis Rheum. 2005;52:3045-3053.

  2. Gonzalez-Gay MA, Gonzalez-Juanatey C, Lopez-Diaz MJ, Pineiro A, Garcia-Porrua C, Miranda-Filloy JA, Ollier WE, Martin J, Llorca J. HLA-DRB1 and persistent chronic inflammation contribute to cardiovascular events and cardiovascular mortality in patients with rheumatoid arthritis. Arthritis Rheum. 2007;57:125-132.

  3. Rodriguez-Rodriguez L, Gonzalez-Juanatey C, Palomino-Morales R, Vazquez-Rodriguez TR, Miranda-Filloy JA, Fernandez-Gutierrez B, Llorca J, Martin J, Gonzalez-Gay MA. TNFA -308 (rs1800629) polymorphism is associated with a higher risk of cardiovascular disease in patients with rheumatoid arthritis. Atherosclerosis 2011;216:125-30.

  4. Samani NJ, Erdmann J, Hall AS, Hengstenberg C, Mangino M, Mayer B, Dixon RJ, Meitinger T, Braund P, Wichmann HE et al. Genomewide association analysis of coronary artery disease. N Engl J Med. 2007;357:443-453.

  5. Kathiresan S, Melander O, Guiducci C, Surti A, Burtt NP, Rieder MJ, Cooper GM, Roos C, Voight BF, Havulinna AS et al. Six new loci associated with blood low-density lipoprotein cholesterol, high-density lipoprotein cholesterol or triglycerides in humans. Nat Genet. 2008;40:189-197.

Disclosure of Interest None Declared

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