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Weak Association Between Genetic Markers of Hyperuricemia and Cardiorenal Outcomes: Insights From the STANISLAS Study Cohort With a 20‐Year Follow‐Up
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) inve...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9238600/ https://www.ncbi.nlm.nih.gov/pubmed/35470676 http://dx.doi.org/10.1161/JAHA.121.023301 |
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author | Kanbay, Mehmet Xhaard, Constance Le Floch, Edith Dandine‐Roulland, Claire Girerd, Nicolas Ferreira, João Pedro Boivin, Jean‐Marc Wagner, Sandra Bacq‐Daian, Delphine Deleuze, Jean‐François Zannad, Faiez Rossignol, Patrick |
author_facet | Kanbay, Mehmet Xhaard, Constance Le Floch, Edith Dandine‐Roulland, Claire Girerd, Nicolas Ferreira, João Pedro Boivin, Jean‐Marc Wagner, Sandra Bacq‐Daian, Delphine Deleuze, Jean‐François Zannad, Faiez Rossignol, Patrick |
author_sort | Kanbay, Mehmet |
collection | PubMed |
description | 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 SLC2A9 gene linked to SUA levels. Carriers of the most associated mutated SLC2A9 allele (rs16890979) 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, rs16890979 was only associated with higher carotid intima‐media thickness. CONCLUSIONS: Our findings demonstrate that rs16890979, a genetic determinant of SUA levels located on the SLC2A9 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. |
format | Online Article Text |
id | pubmed-9238600 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-92386002022-06-30 Weak Association Between Genetic Markers of Hyperuricemia and Cardiorenal Outcomes: Insights From the STANISLAS Study Cohort With a 20‐Year Follow‐Up Kanbay, Mehmet Xhaard, Constance Le Floch, Edith Dandine‐Roulland, Claire Girerd, Nicolas Ferreira, João Pedro Boivin, Jean‐Marc Wagner, Sandra Bacq‐Daian, Delphine Deleuze, Jean‐François Zannad, Faiez Rossignol, Patrick J Am Heart Assoc Original Research 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 SLC2A9 gene linked to SUA levels. Carriers of the most associated mutated SLC2A9 allele (rs16890979) 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, rs16890979 was only associated with higher carotid intima‐media thickness. CONCLUSIONS: Our findings demonstrate that rs16890979, a genetic determinant of SUA levels located on the SLC2A9 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. John Wiley and Sons Inc. 2022-04-26 /pmc/articles/PMC9238600/ /pubmed/35470676 http://dx.doi.org/10.1161/JAHA.121.023301 Text en © 2022 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ (https://creativecommons.org/licenses/by-nc-nd/4.0/) License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made. |
spellingShingle | Original Research Kanbay, Mehmet Xhaard, Constance Le Floch, Edith Dandine‐Roulland, Claire Girerd, Nicolas Ferreira, João Pedro Boivin, Jean‐Marc Wagner, Sandra Bacq‐Daian, Delphine Deleuze, Jean‐François Zannad, Faiez Rossignol, Patrick Weak Association Between Genetic Markers of Hyperuricemia and Cardiorenal Outcomes: Insights From the STANISLAS Study Cohort With a 20‐Year Follow‐Up |
title | Weak Association Between Genetic Markers of Hyperuricemia and Cardiorenal Outcomes: Insights From the STANISLAS Study Cohort With a 20‐Year Follow‐Up |
title_full | Weak Association Between Genetic Markers of Hyperuricemia and Cardiorenal Outcomes: Insights From the STANISLAS Study Cohort With a 20‐Year Follow‐Up |
title_fullStr | Weak Association Between Genetic Markers of Hyperuricemia and Cardiorenal Outcomes: Insights From the STANISLAS Study Cohort With a 20‐Year Follow‐Up |
title_full_unstemmed | Weak Association Between Genetic Markers of Hyperuricemia and Cardiorenal Outcomes: Insights From the STANISLAS Study Cohort With a 20‐Year Follow‐Up |
title_short | Weak Association Between Genetic Markers of Hyperuricemia and Cardiorenal Outcomes: Insights From the STANISLAS Study Cohort With a 20‐Year Follow‐Up |
title_sort | weak association between genetic markers of hyperuricemia and cardiorenal outcomes: insights from the stanislas study cohort with a 20‐year follow‐up |
topic | Original Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9238600/ https://www.ncbi.nlm.nih.gov/pubmed/35470676 http://dx.doi.org/10.1161/JAHA.121.023301 |
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