EXTENDED REPORT

Reduced telomere length in rheumatoid arthritis is independent of disease activity and duration

Sophia E Steer¹, Frances M K Williams², Bernet Kato², Jeffry P Gardner⁵, Paul J Norman³, Margaret A Hall^1,*, Masayuki Kimura⁵, Robert Vaughan⁴, Abraham Aviv⁵, Tim D Spector²

¹ Department of Rheumatology, King’s College London School of Medicine at Guy’s, King’s and St Thomas’, London, UK
² Twin Research and Genetic Epidemiology Unit, Kings College London School of Medicine at Guy’s, King’s and St Thomas’, London, UK
³ Department of Structural Biology, Stanford University School of Medicine, Stanford, California, USA
⁴ Clinical Transplantation Laboratory, Guy’s and St Thomas Foundation Trust and King’s College, London, UK
⁵ The Center of Human Development and Aging, University of Medicine and Dentistry of New Jersey, Newark, New Jersey, USA

Correspondence to:
Professor T Spector
Twin Research and Genetic Epidemiology Unit, Kings College London School of Medicine at Guy’s, King’s and St Thomas’, London SE1 7EH, UK; tim.spector{at}kcl.ac.uk

Background: Rheumatoid arthritis (RA) is associated with reduced lifespan and shortened telomere length in lymphocytes, but the mechanism underlying this is unclear. Telomere loss in white blood cells (WBC) is accelerated by oxidative stress and inflammation in vitro. It was postulated that the accelerated WBC telomere shortening in RA occurs as a result of exposure to chronic inflammation.

Objectives: To measure telomere terminal restriction fragment (TRF) length in a large cohort of RA cases and healthy controls, to explore associations of TRF length with features of disease and with RA-associated HLA-DRB1 alleles.

Methods: WBC and TRF length were measured by Southern blot in DNA from 176 hospital-based RA cases satisfying the 1987 American College of Rheumatology criteria and from 1151 controls. TRF length was compared between cases and controls, and the effects of disease duration, severity and HLA-DRB1 alleles encoding the shared epitope (SE) were assessed.

Results: Age- and sex-adjusted TRF length was significantly shorter in RA cases compared with controls (p<0.001). There was no association between age- and sex-adjusted TRF length and disease duration, C reactive protein or Larsen score. The presence of one or more SE-encoding alleles was associated with reduced adjusted TRF length in RA cases (SE positive vs SE negative cases, p = 0.038), but not in controls.

Conclusion: The reduced TRF length in a large group of patients with RA compared with controls has been shown. The reduction is apparently independent of disease duration and markers of disease severity, but is influenced by HLA-DRB1 genotype.

Abbreviations: CRP, C reactive protein; DAS28, disease activity score calculated using 28 joint count; DMARD, disease-modifying anti-rheumatic drug; mHAQ, modified Health Assessment Questionnaire; RA, rheumatoid arthritis; SE, shared epitope; TRF, terminal restriction fragment; WBC, white blood cell

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