title: Patients with gout have short telomeres compared with healthy participants: association of telomere length with flare frequency and cardiovascular disease in gout.
abstract: OBJECTIVE
  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.
authors.affiliation: Department of Rheumatology and Clinical Immunology, University Medical Centre Utrecht, Utrecht, The Netherlands.|Laboratory of Translational Immunology, University Medical Centre Utrecht, Utrecht, The Netherlands.
authors.forename: N
authors.initials: N
authors.lastname: Vazirpanah
authors.affiliation: Department of Dermatology, University Medical Centre Utrecht, Utrecht, The Netherlands.
authors.forename: L B E
authors.initials: LBE
authors.lastname: Kienhorst
authors.affiliation: Department of Medical Microbiology and Immunology, Rijnstate Hospital, Arnhem, The Netherlands.
authors.forename: E
authors.initials: E
authors.lastname: Van Lochem
authors.affiliation: Department of Rheumatology and Clinical Immunology, University Medical Centre Utrecht, Utrecht, The Netherlands.|Laboratory of Translational Immunology, University Medical Centre Utrecht, Utrecht, The Netherlands.
authors.forename: C
authors.initials: C
authors.lastname: Wichers
authors.affiliation: Department of Rheumatology and Clinical Immunology, University Medical Centre Utrecht, Utrecht, The Netherlands.|Laboratory of Translational Immunology, University Medical Centre Utrecht, Utrecht, The Netherlands.
authors.forename: M
authors.initials: M
authors.lastname: Rossato
authors.affiliation: University of Glasgow, Institute of Cancer Sciences, Wolfson-Wohl Translational Cancer Research Centre, Glasgow, UK.
authors.forename: P G
authors.initials: PG
authors.lastname: Shiels
authors.affiliation: University of Auckland, Auckland, New Zealand.
authors.forename: N
authors.initials: N
authors.lastname: Dalbeth
authors.affiliation: University of Otago, Christchurch, New Zealand.
authors.forename: L K
authors.initials: LK
authors.lastname: Stamp
authors.affiliation: University of Otago, Dunedin, New Zealand.
authors.forename: T R
authors.initials: TR
authors.lastname: Merriman
authors.affiliation: Department of Medical Microbiology and Immunology, Rijnstate Hospital, Arnhem, The Netherlands.
authors.forename: M
authors.initials: M
authors.lastname: Janssen
authors.affiliation: Department of Rheumatology and Clinical Immunology, University Medical Centre Utrecht, Utrecht, The Netherlands.|Laboratory of Translational Immunology, University Medical Centre Utrecht, Utrecht, The Netherlands.
authors.forename: T R D J
authors.initials: TRDJ
authors.lastname: Radstake
authors.affiliation: Department of Rheumatology and Clinical Immunology, University Medical Centre Utrecht, Utrecht, The Netherlands.|Laboratory of Translational Immunology, University Medical Centre Utrecht, Utrecht, The Netherlands.
authors.forename: J Ca
authors.initials: JC
authors.lastname: Broen
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001402:B-Lymphocytes / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism; D002318:Cardiovascular Diseases / Q000453:epidemiology / Q000378:metabolism*; D016022:Case-Control Studies; D003713:Dendritic Cells / Q000378:metabolism; D018450:Disease Progression; D005260:Female; D006073:Gout / Q000453:epidemiology / Q000378:metabolism*; D006801:Humans; D007694:Killer Cells, Natural / Q000378:metabolism; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000378:metabolism; D019098:Telomerase / Q000235:genetics*; D016615:Telomere / Q000378:metabolism*
chemical_list: C509186:TERT protein, human; D019098:Telomerase
keywords: Cardiovascular Disease; Gout; Inflammation