Gout patients have shorter telomeres; telomere length linked to gouty flares, CV disease
Telomeres appear to be shorter in patients with gout than in healthy individuals, indicating increased cellular senescence, according to a study. In gout, telomere shortening is associated with flare frequency and cardiovascular (CV) disease.
To investigate whether inflammation in gout accelerated senescence and thereby enhanced the risk of CV disease, researchers evaluated replicative senescence by quantifying telomere length (TL) in a discovery cohort of 145 gout patients and 273 healthy individuals from The Netherlands. Results were subsequently validated in another cohort of 474 gout patients and 293 healthy individuals from New Zealand.
Other assessments included the effect of CV disease on TL, potential temporal difference in TL and telomerase activity, as well as the TL of CD4+ and CD8+ T lymphocytes, B lymphocytes, monocytes, natural killer cells and plasmacytoid dendritic cells.
TL in peripheral blood mononuclear cells (PBMCs) of healthy donors was found to decrease over time, reflecting normal ageing. In contrast, gout patients demonstrated shorter telomeres (p=0.001), with the extent of telomere erosion being higher at any age compared with healthy counterparts at any age (p<0.0001).
The shortest telomeres were observed in gout patients with CV disease, with TL shown to be an independent risk factor for CV disease in patients with gout (p=0.001). Moreover, TL was inversely associated with the number of gouty flares (p=0.005).
Findings of the present study indicate shorter TL to be a feature of gout, with TL independently associated with flare frequency and cardiovascular disease.
“These data suggest that intensive treatment of gout may prevent replicative senescence and subsequently reduce the associated cardiovascular risk. However, large prospective studies are needed to test this possibility,” researchers said.
A rheumatic disease characterized by deposition of monosodium urate crystals in and around the joints, gout is the most common inflammatory arthritis in men aged >40 years. Affected patients have recurrent episodes of acute joint inflammation and inflammatory mediators, such as interleukin 8, even without clinically apparent inflammatory disease. [Lancet 2016;6736:1–14; Arthritis Rheum 2006;54:2688–96; Curr Opin Rheumatol 2010;22:165–72; Metab Clin Exp 2015;67:3303–13]