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


OBJECTIVE
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.


CONCLUSIONS
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.
Steer
Sophia E
SE
Department of Rheumatology, Twin Research and Genetic Epidemiology Unit, Kings College London School of Medicine at Guy's, King's and St Thomas', London SE1 7EH, UK.
Williams
Frances M K
FM
Kato
Bernet
B
Gardner
Jeffry P
JP
Norman
Paul J
PJ
Hall
Margaret A
MA
Kimura
Masayuki
M
Vaughan
Robert
R
Aviv
Abraham
A
Spector
Tim D
TD
D000367:Age Factors; D000368:Aged; D001172:Arthritis, Rheumatoid / Q000235:genetics*; D016022:Case-Control Studies; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006684:HLA-DR Antigens / Q000235:genetics; D059811:HLA-DRB1 Chains; D006801:Humans; D008297:Male; D008875:Middle Aged; D012720:Severity of Illness Index; D012737:Sex Factors; D016615:Telomere / Q000648:ultrastructure*; D013997:Time Factors
D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains