RESEARCH - Reduced telomere length in RA is independent of disease activity and duration

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Ann Rheum Dis. Published Online First: 17 November 2006.

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Extended Report

Reduced telomere length in rheumatoid arthritis is independent of disease

activity and duration

Sophia Steer 1, Frances M.K. 1, Bernet Kato 1, Jeffry P Gardner 2,

J Norman 3, Margaret A Hall 1, Masayuki Kimura 2, Vaughan 1,

Abraham Aviv 2 and Tim Spector 1*

1 Kings College London School of Medicine, United Kingdom

2 The Center of Human Development and Aging, University of Medicine and

Dentistry of New Jersey, Newar, United States

3 Dept of Structural Biology, Stanford University School of Medicine,

Stanford,, United States

Abstract

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 is accelerated by oxidative stress and

inflammation in vitro. We postulated that accelerated white blood cell

telomere shortening in rheumatoid arthritis 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: We measured white blood cell (WBC) terminal restriction fragment

(TRF) length by Southern blot in DNA from 176 hospital-based RA cases

satisfying the 1987 ACR criteria and 1151 healthy controls. We compared TRF

length between cases and controls, and assessed the effects of disease

duration, severity and HLA-DRB1 alleles encoding the shared epitope (SE).

Results: Age and sex-adjusted TRF length was significantly shorter in RA

cases compared to controls (p < 0.001). There was no association between

age- and sex-adjusted TRF length and disease duration, CRP 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: We have demonstrated reduced TRF length in a large group of RA

patients compared to controls. The reduction is apparently independent of

disease duration and markers of disease severity but is influenced by

HLA-DRB1 genotype.

http://ard.bmj.com/cgi/content/abstract/ard.2006.059188v2?papetoc

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