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.
- 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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↵* These authors contributed equally to this work.
Published Online First 17 November 2006
Funding: SS was supported by the arthritis research campaign (arc) and NHS R&D funding from Lewisham Hospital NHS Trust. The study was also supported by NHS R&D funding from Guy’s and St Thomas’ NHS Trust. MAH was supported by the arthritis research campaign (arc). AA aging research is supported by NIH grants AG021593 and AG020132, and The Healthcare Foundation of New Jersey.
Competing interests: None.
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