The lp13.3 genomic region -rs599839- is associated with endothelial dysfunction in patients with rheumatoid arthritis

Arthritis Research & Therapy

Raquel López-Mejías⁵  Carlos González-Juanatey¹  Mercedes García-Bermúdez³  Santos Castañeda⁴  José A Miranda-Filloy⁶  Ricardo Blanco⁵  Javier Llorca²  Javier Martín³  Miguel A González-Gay⁵ 

[1] Cardiology Division, Hospital Xeral-Calde, Lugo, Spain

[2] Department of Epidemiology and Computational Biology, School of Medicine, University of Cantabria, and CIBER Epidemiología y Salud Pública (CIBERESP), IFIMAV, Santander, Spain

[3] Instituto de Parasitología y Biomedicina López-Neyra, IPBLN-CSIC, Granada, Spain

[4] Rheumatology Department, Hospital Universitario la Princesa, IIS-Princesa, Madrid, Spain

[5] Department of Rheumatology, Hospital Universitario Marqués de Valdecilla, IFIMAV, Santander, Spain

[6] Division of Rheumatology, Hospital Xeral-Calde, Lugo, Spain

关键词: rheumatoid arthritis;    rs599839;    endothelial dysfunction;    cardiovascular disease;    atherosclerosis;   

Others  :  1098232
DOI  :  10.1186/ar3755

 received in 2011-10-11, accepted in 2012-03-01,  发布年份 2012

【 摘 要 】

Introduction

Rheumatoid arthritis (RA) is an inflammatory disease associated with accelerated atherosclerosis and high risk of cardiovascular (CV) disease. Since genome-wide association studies demonstrated association between rs599839 polymorphism and coronary artery disease, in the present study we assessed the potential association of this polymorphism with endothelial dysfunction, an early step in atherogenesis.

Methods

A total of 128 RA patients without history of CV events were genotyped for rs599839 A/G polymorphism. The 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.

【 授权许可】

   
2012 López Mejías et al.; licensee BioMed Central Ltd.

【 参考文献 】

• [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]Gonzalez-Juanatey C, Testa A, Garcia-Castelo A, Garcia-Porrua C, Llorca J, Vidan J, Hajeer AH, Ollier WE, Mattey DL, Gonzalez-Gay MA: HLA-DRB1 status affects endothelial function in treated patients with rheumatoid arthritis. Am J Med 2003, 114:647-652.
• [5]Vaudo G, Marchesi S, Gerli R, Allegrucci R, Giordano A, Siepi D, Pirro M, Shoenfeld Y, Schillaci G, Mannarino E: Endothelial dysfunction in young patients with rheumatoid arthritis and low disease activity. Ann Rheum Dis 2004, 63:31-35.
• [6]Samani NJ, Braund PS, Erdmann J, Gotz A, Tomaszewski M, Linsel-Nitschke P, Hajat C, Mangino M, Hengstenberg C, Stark K, Ziegler A, Caulfield M, Burton PR, Schunkert H, Tobin MD: The novel genetic variant predisposing to coronary artery disease in the region of the PSRC1 and CELSR2 genes on chromosome 1 associates with serum cholesterol. J Mol Med (Berl) 2008, 86:1233-1241.
• [7]Samani NJ, Erdmann J, Hall AS, Hengstenberg C, Mangino M, Mayer B, Dixon RJ, Meitinger T, Braund P, Wichmann HE, Barrett JH, König IR, Stevens SE, Szymczak S, Tregouet DA, Iles MM, Pahlke F, Pollard H, Lieb W, Cambien F, Fischer M, Ouwehand W, Blankenberg S, Balmforth AJ, Baessler A, Ball SG, Strom TM, Braenne I, Gieger C, Deloukas P, et al.: Genomewide association analysis of coronary artery disease. N Engl J Med 2007, 357:443-453.
• [8]Kathiresan S, Melander O, Guiducci C, Surti A, Burtt NP, Rieder MJ, Cooper GM, Roos C, Voight BF, Havulinna AS, Wahlstrand B, Hedner T, Corella D, Tai ES, Ordovas JM, Berglund G, Vartiainen E, Jousilahti P, Hedblad B, Taskinen MR, Newton-Cheh C, Salomaa V, Peltonen L, Groop L, Altshuler DM, Orho-Melander M: Six new loci associated with blood low-density lipoprotein cholesterol, high-density lipoprotein cholesterol or triglycerides in humans. Nat Genet 2008, 40:189-197.
• [9]Sandhu MS, Waterworth DM, Debenham SL, Wheeler E, Papadakis K, Zhao JH, Song K, Yuan X, Johnson T, Ashford S, Inouye M, Luben R, Sims M, Hadley D, McArdle W, Barter P, Kesäniemi YA, Mahley RW, McPherson R, Grundy SM, Wellcome Trust Case Control Consortium, Bingham SA, Khaw KT, Loos RJ, Waeber G, Barroso I, Strachan DP, Deloukas P, Vollenweider P, Wareham NJ, Mooser V: LDL-cholesterol concentrations: a genome-wide association study. Lancet 2008, 371:483-491.
• [10]Willer CJ, Sanna S, Jackson AU, Scuteri A, Bonnycastle LL, Clarke R, Heath SC, Timpson NJ, Najjar SS, Stringham HM, Strait J, Duren WL, Maschio A, Busonero F, Mulas A, Albai G, Swift AJ, Morken MA, Narisu N, Bennett D, Parish S, Shen H, Galan P, Meneton P, Hercberg S, Zelenika D, Chen WM, Li Y, Scott LJ, Scheet PA, et al.: Newly identified loci that influence lipid concentrations and risk of coronary artery disease. Nat Genet 2008, 40:161-169.
• [11]Nakayama M, Nakajima D, Nagase T, Nomura N, Seki N, Ohara O: Identification of high-molecular-weight proteins with multiple EGF-like motifs by motif-trap screening. Genomics 1998, 51:27-34.
• [12]NCI-NHGRI Working Group on Replication in Association Studies, Chanock SJ, Manolio T, Boehnke M, Boerwinkle E, Hunter DJ, Thomas G, Hirschhorn JN, Abecasis G, Altshuler D, Bailey-Wilson JE, Brooks LD, Cardon LR, Daly M, Donnelly P, Fraumeni JF Jr, Freimer NB, Gerhard DS, Gunter C, Guttmacher AE, Guyer MS, Harris EL, Hoh J, Hoover R, Kong CA, Merikangas KR, Morton CC, Palmer LJ, Phimister EG, Rice JP, et al.: Replicating genotype-phenotype associations. Nature 2007, 447:655-660.
• [13]Arnett FC, Edworthy SM, Bloch DA, McShane DJ, Fries JF, Cooper NS, Healey LA, Kaplan SR, Liang MH, Luthra HS, Medsger TA, Mitchell DM, Neustadt DH, Pinals RS, Schaller JG, Sharp JT, Wilder RL, Hunder GG: The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis. Arthritis Rheum 1988, 31:315-324.
• [14]Gonzalez-Gay MA, Gonzalez-Juanatey C, Vazquez-Rodriguez TR, Martin J, Llorca J: Endothelial dysfunction, carotid intima-media thickness, and accelerated atherosclerosis in rheumatoid arthritis. Semin Arthritis Rheum 2008, 38:67-70.
• [15]Ter Avest E, Stalenhoef AF, de Graaf J: What is the role of non-invasive measurements of atherosclerosis in individual cardiovascular risk prediction? Clin Sci (Lond) 2007, 112:507-516.