Joint Bone Spine 78 (2011) 184–187 Original article Increased production of asymmetric dimethylarginine (ADMA) in ankylosing spondylitis: Association with other clinical and laboratory parameters Ádám Kemény-Beke a , Rudolf Gesztelyi b , Nóra Bodnár c , Judit Zsuga d , György Kerekes e , Miklós Zsuga f , Bernadett Biri f , Sándor Kéki f , Péter Szodoray g , András Berta a , Zoltán Szekanecz c,∗ , Sándor Szántó c a Department of Ophthalmology, University of Debrecen, Medical and Health Science Center, Debrecen, 4032, Hungary b Department of Pharmacology, University of Debrecen, Medical and Health Science Center, Debrecen, 4032, Hungary c Department of Rheumatology, Institute of Medicine, University of Debrecen, Medical and Health Science Center, 98 Nagyerdei str, Debrecen, 4032, Hungary d Department of Neurology, University of Debrecen, Medical and Health Science Center, Debrecen, 4032, Hungary e Third Department of Medicine, University of Debrecen, Medical and Health Science Center, Debrecen, 4032, Hungary f Department of Applied Chemistry, Center of Arts, Humanities and Sciences, University of Debrecen, Debrecen, 4032, Hungary g Institute of Immunology, Rikshospitalet, University of Oslo, Oslo, Norway article info Article history: Accepted 21 May 2010 Keywords: Ankylosing spondylitis ADMA Atherosclerosis Cardiovascular disease abstract Objective: Asymmetric dimethylarginine (ADMA) has been associated with atherosclerosis, vascular dis- eases and, recently, also with arthritis including rheumatoid arthritis (RA) and ankylosing spondylitis (AS). Methods: Serum ADMA, arginine and symmetric dimethylarginine (SDMA) levels were assessed by liquid chromatography in 61 AS and 26 osteoarthritis (OA) patients with no known cardiovascular disease. Results: Serum ADMA levels were significantly increased in AS compared to OA patients (0.95 ± 0.17 M versus 0.70 ± 0.25 M; p < 0.001). There were no differences in serum arginine and SDMA levels. Serum ADMA levels also positively correlated with age (R = 0.258; p = 0.043), body mass index (R = 0.368; p = 0.003), erythrocyte sedimentation rate (R = 0.329; p = 0.009) and ADMA levels negative correlated with chest expansion (R = -0.251; p = 0.04). No correlations were found between ADMA levels and dis- ease duration, pain intensity, BASDAI, BASFI, BASMI, quality of life, CRP, HLA-B27 positivity, endothelial dysfunction or carotid atherosclerosis. Conclusion: ADMA may serve as a marker of systemic inflammation and may reflect functional immobility in AS. Further studies are needed to assess the possible role of ADMA in AS and AS-related vascular disease. © 2010 Société franc ¸ aise de rhumatologie. Published by Elsevier Masson SAS. All rights reserved. 1. Introduction Ankylosing spondylitis (AS) is a chronic immuno-inflammatory rheumatic disease eventually leading to physical disability [1]. Accelerated atherosclerosis and increased cardiovascular mor- bidity and mortality have been associated with numerous inflammatory diseases including rheumatoid arthritis (RA), lupus and scleroderma [2–4]. AS may also be associated with vascular dis- ease, which is considered as an extraarticular feature of the disease [5]. Endothelial dysfunction has been detected in AS patients [6,7], however overt carotid atherosclerosis could not be identified [6,8]. An EULAR recommendation for the prevention and management of cardiovascular disease associated with arthritis including AS has recently been published [9]. ∗ Corresponding author. Tel.: +36 52 255 091; fax: +36 52 414 489. E-mail addresses: szekanecz.zoltan@med.unideb.hu, szekanecz@hotmail.com (Z. Szekanecz). Asymmetric dimethylarginine (ADMA) has emerged as a link between insulin resistance, atherosclerosis and vascular disease [10–13]. ADMA is the major endogenous inhibitor of solu- ble nitric oxide (NO) synthase that has been associated with carotid atherosclerosis, acute coronary syndrome and cerebrovas- cular disease [11–13]. As NO promotes vasodilatation, ADMA might be deleterious by inhibiting this effect [14,15]. Homocys- teine and LDL cholesterol (LDL-C), two major risk factors for atherosclerosis and cardiovascular disease, also leads to increased ADMA production and retention [16–18]. Furthermore, statins also seem to be less efficient in patients with high ADMA lev- els [19,20]. Recently, increased ADMA production was reported in RA patients [21,22]. ADMA levels were inversely correlated with coronary flow reserve in RA [22]. Very recently, Sari et al. [23] reported increased production of ADMA in 48 AS patients without classical cardiovascular risk factors in comparison to healthy controls. However, in that study AS patients were not compared to OA patients and SDMA and l-arginine were not mea- sured. 1297-319X/$ – see front matter © 2010 Société franc ¸ aise de rhumatologie. Published by Elsevier Masson SAS. All rights reserved. doi:10.1016/j.jbspin.2010.05.009