Weak Association Between Genetic Markers of Hyperuricemia and Cardiorenal Outcomes: Insights From the STANISLAS Study Cohort With a 20‐Year Follow‐Up

• Tipo: Artigo em Revista Científica Internacional
• Data: 2022

Autores

Kanbay, M (Autor) Outra; Xhaard, C (Autor) Outra; Le Floch, E (Autor) Outra; Dandine¿Roulland, C (Autor) Outra; Girerd, N (Autor) Outra; Ferreira, JP (Autor) FMUP; Boivin, J (Autor) Outra; Wagner, S (Autor) Outra; Bacq¿Daian, D (Autor) Outra; Deleuze, J (Autor) Outra; Zannad, F (Autor) Outra; Rossignol, P (Autor) Outra

Revista

Título: Journal of the American Heart Association

Vol. 118

ISSN: 2047-9980

Editora: Wiley-Blackwell

Outras Informações

ID Authenticus: P-00W-TW1

DOI: 10.1161/jaha.121.023301

Abstract (EN): <jats:sec xml:lang="en"> <jats:title>Background</jats:title> <jats:p xml:lang="en">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.</jats:p> </jats:sec> <jats:sec xml:lang="en"> <jats:title>Methods and Results</jats:title> <jats:p xml:lang="en"> 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 <jats:italic>SLC2A9</jats:italic> gene linked to SUA levels. Carriers of the most associated mutated <jats:italic>SLC2A9</jats:italic> allele ( <jats:italic>rs16890979</jats:italic> ) 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, <jats:italic>rs16890979</jats:italic> was only associated with higher carotid intima¿media thickness. </jats:p> </jats:sec> <jats:sec xml:lang="en"> <jats:title>Conclusions</jats:title> <jats:p xml:lang="en"> Our findings demonstrate that <jats:italic>rs16890979</jats:italic> , a genetic determinant of SUA levels located on the <jats:italic>SLC2A9</jats:italic> 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. </jats:p> </jats:sec>

Idioma: Inglês

Tipo (Avaliação Docente): Científica