Weak Association Between Genetic Markers of Hyperuricemia and Cardiorenal Outcomes: Insights From the STANISLAS Study Cohort With a 20-Year Follow-Up.
Fiche publication
Date publication
avril 2022
Journal
Journal of the American Heart Association
Auteurs
Membres identifiés du Cancéropôle Est :
Pr ROSSIGNOL Patrick
Tous les auteurs :
Kanbay M, Xhaard C, Le Floch E, Dandine-Roulland C, Girerd N, Ferreira JP, Boivin JM, Wagner S, Bacq-Daian D, Deleuze JF, Zannad F, Rossignol P
Lien Pubmed
Résumé
Background Hyperuricemia is associated with poor cardiovascular outcomes, although it is uncertain whether this relationship is causal in nature. This study aimed to: (1) assess the heritability of serum uric acid (SUA) levels, (2) conduct a genome-wide association study on SUA levels, and (3) investigate the association between certain single-nucleotide polymorphisms and target organ damage. Methods and Results The STANISLAS (Suivi Temporaire Annuel Non-Invasif de la Santé des Lorrains Assurés Sociaux) study cohort is a single-center longitudinal cohort recruited between 1993 and 1995 (visit 1), with a last visit (visit 4 [V4]) performed ≈20 years apart. Serum lipid profile, SUA, urinary albumin/creatinine ratio, estimated glomerular filtration rate, 24-hour ambulatory blood pressure monitoring, transthoracic echocardiography, pulse wave velocity, and genotyping for each participant were assessed at V4. A total of 1573 participants were included at V4, among whom 1417 had available SUA data at visit 1. Genome-wide association study results highlighted multiple single-nucleotide polymorphisms on the gene linked to SUA levels. Carriers of the most associated mutated allele () had significantly lower SUA levels. Although SUA level at V4 was highly associated with diabetes, prediabetes, higher body mass index, CRP (C-reactive protein) levels, estimated glomerular filtration rate variation (visit 1-V4), carotid intima-media thickness, and pulse wave velocity, was only associated with higher carotid intima-media thickness. Conclusions Our findings demonstrate that , a genetic determinant of SUA levels located on the gene, is associated with carotid intima-media thickness despite significant associations between SUA levels and several clinical outcomes, thereby lending support to the hypothesis of a link between SUA and cardiovascular disease.
Mots clés
cardiovascular disease, genome‐wide association study, single‐nucleotide polymorphism, uric acid
Référence
J Am Heart Assoc. 2022 Apr 26;:e023301