Associations between serum urate and telomere length and inflammation markers: Evidence from UK Biobank cohort

Abstract

ObjectiveHyperuricemia and gout have become gradually more common. The effect of serum urate on organism aging and systematic inflammation is not determined. This study aims to evaluate whether serum urate is causally associated with cellular aging markers and serum inflammation markers.MethodsA Mendelian randomization study was performed on summary-level data from the largest published genome-wide association studies. Single nucleotide polymorphisms with a genome-wide significance level were selected as instrumental variables for leukocyte telomere length (LTL), and serum soluble makers of inflammation (CRP, IL-6, TNF-α, and IGF-1). Standard inverse variance weighted (IVW) method was used as the primary statistical method. The weighted median, MR-Egger regression, and MR-PRESSO methods were used for sensitivity analysis.ResultsAn inverse causal association of genetically predicted serum urate levels and LTL was found using IVW method (OR: 0.96, 95%CI 0.95, 0.97; β=-0.040; SE=0.0072; P=4.37×10-8). The association was also supported by MR results using MR-Egger method and weighted median method. The MR-PRESSO analysis and leave-one-out sensitivity analysis supported the robustness of the combined results. In terms of other aging-related serum biomarkers, there was no evidence supporting a causal effect of serum urate on CRP, IL-6, TNF-α, or IGF-1 levels.ConclusionsSerum urate levels are negatively associated with telomere length but are not associated with serum soluble indicators of inflammation. Telomere length may be a critical marker that reflects urate-related organismal aging and may be a mechanism in the age-related pathologies and mortality caused by hyperuricemia.

Breaking down causes, consequences, and mediating effects of telomere length variation on human health

“…Urate levels, also retained as a relevant predictor of LTL by the Lasso regression analysis, displayed a negative association with LTL ( ). As previously reported [ 31 ], MR analyses showed that elevated urate levels decreased LTL ( ), possibly due to increased cellular stress and reactive oxygen species production [ 32 ] (Fig. 2 f).…”

Breaking down causes, consequences, and mediating effects of age-related telomere shortening on human health

“…Lasso analysis retained both urate (β = −0.025; p = 2.1e−44) and cystatin C (β = −0.033; p = 2.2e−75) levels as relevant predictors of LTL (Table 1), highlighting the link between kidney function and LTL. As previously reported [45], MR analyses showed that elevated urate levels decreased LTL (αT →LT L = −0.042; p = 9.4e−18), possibly due to increased cellular stress and reactive oxygen species production [46]. The urate-LTL association was significantly mediated by CRP, confirming the role of inflammation in this process (P M = 34.7%; 95%-CI[17.1%; 55.6%]).…”

Robust evidence supports a causal link between higher birthweight and longer telomere length: a mendelian randomization study

“…A cohort study (Wei et al, 2021) from China also found a relationship between prematernal overweight and shorter neonatal telomeres. The specific mechanisms still require elucidation but could involve pathways influencing metabolism, growth factors, and inflammation (Movérare-Skrtic et al, 2009;Xu et al, 2014;Lv et al, 2022). Mendelian randomization analyses to investigate associations between birth weight and telomere length.…”