Genetic contributors to serum uric acid levels in Mexicans and their effect on premature coronary artery disease.

Abstract

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:

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:

Only two loci were associated with SUA levels: SLC2A9 (β = -0.47 mg/dl, P = 1.57 × 10-42 for lead SNP rs7678287) and ABCG2 (β = 0.23 mg/dl, P = 2.42 × 10-10 for lead SNP rs2231142). No significant interaction between SLC2A9 rs7678287 and ABCG2 rs2231142 genotypes and obesity was observed. However, a significant ABCG2 rs2231142 genotype*sex interaction (P = 0.001) was observed in adults but not in children. Although SUA levels were associated with premature CAD, metabolic syndrome and decreased glomerular filtration rate (eGFR), only ABCG2 rs2231142 was associated with decreased eGFR in the premature CAD group.

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.

• Authors: Luis R Macias-Kauffer, Hugo Villamil-Ramírez, Paola León-Mimila, Leonor Jacobo-Albavera, Carlos Posadas-Romero, Rosalinda Posadas-Sánchez, Blanca E López-Contreras, Sofía Morán-Ramos, Sandra Romero-Hidalgo, Víctor Acuña-Alonzo, Blanca E Del-Río-Navarro, Maria-Cátira Bortolini, Carla Gallo, Gabriel Bedoya, Francisco Rothhammer, Rolando González-Jose, Andrés Ruiz-Linares, Christopher R Stephens, Rafael Velazquez-Cruz, Cecilia Fernández Del Valle-Laisequilla, Juan G Reyes-García, Lina M Barranco Garduño, Miriam Del C Carrasco-Portugal, Francisco J Flores-Murrieta, Gilberto Vargas-Alarcón, Carlos A Aguilar-Salinas, Teresa Villarreal-Molina, Samuel Canizales-Quinteros
• Journal: International journal of cardiology (Int J Cardiol) Vol. 279 Pg. 168-173 (Mar 15 2019) ISSN: 1874-1754 [Electronic] Netherlands
• PMID: 30305239 (Publication Type: Journal Article)
• Copyright: Copyright © 2018 Elsevier B.V. All rights reserved.

Chemical References

• Biomarkers
• Uric Acid

Topics

• Adolescent
• Adult
• Aged
• Aged, 80 and over
• Biomarkers (blood)
• Child
• Coronary Artery Disease (blood, epidemiology, genetics)
• 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