Orsolya I. Gaal (1,2), Georgiana Cabau (1), Medeea Badii (1,2), Ancuta R. Straton (1), Nica Valentin (1), Maria Muntiu (1), HINT Consortium, Cristina Pamfil (3), Leo A.B. Joosten (1,2), Tania O. Crisan (1,2)
Affiliation(s):
1. Department of Medical Genetics, Iuliu Hațieganu University of Medicine and Pharmacy, Cluj-Napoca Romania;
2. Department of Internal Medicine, Radboud University Medical Center, Nijmegen, The Netherlands;
3. Department of Rheumatology, Iuliu Hațieganu University of Medicine and Pharmacy, Cluj- Napoca
Romania;
Introduction: Gout is an inflammatory condition with a high prevalence. It is characterized by recurrent flares driven by monosodium urate (MSU) crystals, which activate the NLRP3 inflammasome and induce the release of pro-inflammatory cytokines such as IL-1β or IL-6. Telomeres are repetitive DNA sequences at the ends of chromosomes and their main function is to prevent the loss of important genetic information during cell division. Telomere length (TL) is a key biomarker of biological aging and has been implicated in various chronic diseases, including gout. Hyperuricemia, the main risk factor for gout, is associated with increased production of reactive oxygen species (ROS), which damage DNA and accelerate telomere shortening. Moreover, the persistent inflammation observed in gout accelerates oxidative stress, a major driver of telomere attrition. Here, we investigate whether telomere length differs among gout patients, hyperuricemic controls, and normouricemic controls. We also examined whether telomere length correlates with the cytokine production capacity of mononuclear cells as higher levels of pro-inflammatory cytokines may be linked to shorter TL in immune cells.
Materials and methods: The study was performed in the HINT study groups (patients with gout n=81, hyperuricemia n=73 and normouricemic controls n=76, Romania). Genomic DNA was isolated from whole blood and average telomere length was determined using the Absolute Human Telomere Length Quantification qPCR Assay Kit (ScienCell, CA, USA) following the supplier's instructions. Ex vivo functional assays were performed, consisting of PBMC stimulations with C16+MSU (TLR2/NLRP3 inflammasome activator) or LPS (TLR4 ligand) for 24h. Cytokines were assessed by ELISA.
Results: No significant differences in TL were observed between the groups. When stratifying the analysis by distinct age groups, variations in TL were detected, yet no overall correlation was found between TL serum urate levels, or BMI in any of the examined cohorts. Furthermore, no association was identified between TL and the pro-inflammatory cytokine IL-1b or the anti-inflammatory IL-1Ra production of peripheral blood mononuclear cells (PBMCs) in the presence of different stimuli.
Conclusions: Our findings suggest that telomere length does not significantly differ between gout patients, hyperuricemic controls, and normouricemic controls, nor does it correlate with serum urate levels, BMI, or pro-inflammatory cytokine production. Given the relatively small study group sizes assesed so far and the complexity of telomere dynamics with inter-individual variability, larger cohorts may be required to detect potential associations and fully elucidate the role of telomere length in gout and hyperuricemia inflammation.
Key words: gout, telomere length, urate, cytokine