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Patients with gout have short telomeres compared with healthy participants: association of telomere length with flare frequency and cardiovascular disease in gout
  1. N Vazirpanah1,2,
  2. L B E Kienhorst3,
  3. E Van Lochem4,
  4. C Wichers1,2,
  5. M Rossato1,2,
  6. P G Shiels5,
  7. N Dalbeth6,
  8. L K Stamp7,
  9. T R Merriman8,
  10. M Janssen4,
  11. T R D J Radstake1,2,
  12. J CA Broen1,2
  1. 1Department of Rheumatology and Clinical Immunology, University Medical Centre Utrecht, Utrecht, The Netherlands
  2. 2Laboratory of Translational Immunology, University Medical Centre Utrecht, Utrecht, The Netherlands
  3. 3Department of Dermatology, University Medical Centre Utrecht, Utrecht, The Netherlands
  4. 4Department of Medical Microbiology and Immunology, Rijnstate Hospital, Arnhem, The Netherlands
  5. 5University of Glasgow, Institute of Cancer Sciences, Wolfson-Wohl Translational Cancer Research Centre, Glasgow, UK
  6. 6University of Auckland, Auckland, New Zealand
  7. 7University of Otago, Christchurch, New Zealand
  8. 8University of Otago, Dunedin, New Zealand
  1. Correspondence to J C A Broen, WKZ Lundlaan 6 KC 02.085.2 P.O. Box 85090, Utrecht 3508 AB, The Netherlands; j.c.a.broen{at}umcutrecht.nl

Abstract

Aim and background Chronic inflammation associates with increased senescence, which is a strong predictor for cardiovascular disease. We hypothesised that inflammation accelerates senescence and thereby enhances the risk of cardiovascular disease in gout.

Methods We assessed replicative senescence by quantifying telomere length (TL) in a discovery cohort of 145 Dutch patients with gout and 273 healthy individuals and validated our results in 474 patients with gout and 293 healthy participants from New Zealand. Subsequently, we investigated the effect of cardiovascular disease on TL of all participants. Also, we measured TL of CD4+ and CD8+ T lymphocytes, B lymphocytes, monocytes, natural killer cells and plasmacytoid dendritic cells. Additionally, we assessed the potential temporal difference in TL and telomerase activity.

Results TL in PBMCs of healthy donors decreased over time, reflecting normal ageing. Patients with gout demonstrated shorter telomeres (p=0.001, R2=0.01873). In fact, the extent of telomere erosion in patients with gout was higher at any age compared with healthy counterparts at any age (p<0.0001, R2=0.02847). Patients with gout with cardiovascular disease had the shortest telomeres and TL was an independent risk factor for cardiovascular disease in patients with gout (p=0.001). TL was inversely associated with the number of gouty flares (p=0.005).

Conclusions Patients with gout have shorter telomeres than healthy participants, reflecting increased cellular senescence. Telomere shortening was associated with the number of flares and with cardiovascular disease in people with gout.

  • Gout
  • Inflammation
  • Cardiovascular Disease

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