Genetic contributors to serum uric acid levels in Mexicans and their effect on premature coronary artery disease.
Adolescent
Adult
Aged
Aged, 80 and over
Biomarkers
/ blood
Child
Coronary Artery Disease
/ blood
Female
Genome-Wide Association Study
/ methods
Humans
Male
Mendelian Randomization Analysis
/ methods
Mexico
/ epidemiology
Middle Aged
Polymorphism, Single Nucleotide
/ genetics
Uric Acid
/ blood
Young Adult
Coronary artery disease
Genetics
Uric acid
Journal
International journal of cardiology
ISSN: 1874-1754
Titre abrégé: Int J Cardiol
Pays: Netherlands
ID NLM: 8200291
Informations de publication
Date de publication:
15 Mar 2019
15 Mar 2019
Historique:
received:
16
02
2018
revised:
23
08
2018
accepted:
25
09
2018
pubmed:
12
10
2018
medline:
18
12
2019
entrez:
12
10
2018
Statut:
ppublish
Résumé
Serum uric acid (SUA) is a heritable trait associated with cardiovascular risk factors and coronary artery disease (CAD). Genome wide association studies (GWAS) have identified several genes associated with SUA, mainly in European populations. However, to date there are few GWAS in Latino populations, and the role of SUA-associated single nucleotide polymorphisms (SNPs) in cardiovascular disease has not been studied in the Mexican population. We performed genome-wide SUA association study in 2153 Mexican children and adults, evaluated whether genetic effects were modified by sex and obesity, and used a Mendelian randomization approach in an independent cohort to study the role of SUA modifying genetic variants in premature CAD. Only two loci were associated with SUA levels: SLC2A9 (β = -0.47 mg/dl, P = 1.57 × 10 SUA elevation was independently associated with premature CAD, metabolic syndrome and decreased eGFR in the Mexican population. However, a Mendelian randomization approach using the lead SUA-associated SNPs (SLC2A9 and ABCG2) did not support a causal role of elevated SUA levels for premature CAD.
Sections du résumé
BACKGROUND
BACKGROUND
Serum uric acid (SUA) is a heritable trait associated with cardiovascular risk factors and coronary artery disease (CAD). Genome wide association studies (GWAS) have identified several genes associated with SUA, mainly in European populations. However, to date there are few GWAS in Latino populations, and the role of SUA-associated single nucleotide polymorphisms (SNPs) in cardiovascular disease has not been studied in the Mexican population.
METHODS
METHODS
We performed genome-wide SUA association study in 2153 Mexican children and adults, evaluated whether genetic effects were modified by sex and obesity, and used a Mendelian randomization approach in an independent cohort to study the role of SUA modifying genetic variants in premature CAD.
RESULTS
RESULTS
Only two loci were associated with SUA levels: SLC2A9 (β = -0.47 mg/dl, P = 1.57 × 10
CONCLUSIONS
CONCLUSIONS
SUA elevation was independently associated with premature CAD, metabolic syndrome and decreased eGFR in the Mexican population. However, a Mendelian randomization approach using the lead SUA-associated SNPs (SLC2A9 and ABCG2) did not support a causal role of elevated SUA levels for premature CAD.
Identifiants
pubmed: 30305239
pii: S0167-5273(18)31073-8
doi: 10.1016/j.ijcard.2018.09.107
pii:
doi:
Substances chimiques
Biomarkers
0
Uric Acid
268B43MJ25
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
168-173Informations de copyright
Copyright © 2018 Elsevier B.V. All rights reserved.