TY - JOUR
T1 - Genetic contributors to serum uric acid levels in Mexicans and their effect on premature coronary artery disease
AU - Macias-Kauffer, Luis R.
AU - Villamil-Ramírez, Hugo
AU - León-Mimila, Paola
AU - Jacobo-Albavera, Leonor
AU - Posadas-Romero, Carlos
AU - Posadas-Sánchez, Rosalinda
AU - López-Contreras, Blanca E.
AU - Morán-Ramos, Sofía
AU - Romero-Hidalgo, Sandra
AU - Acuña-Alonzo, Víctor
AU - del-Río-Navarro, Blanca E.
AU - Bortolini, Maria Cátira
AU - Gallo, Carla
AU - Bedoya, Gabriel
AU - Rothhammer, Francisco
AU - González-Jose, Rolando
AU - Ruiz-Linares, Andrés
AU - Stephens, Christopher R.
AU - Velazquez-Cruz, Rafael
AU - Fernández del Valle-Laisequilla, Cecilia
AU - Reyes-García, Juan G.
AU - Barranco Garduño, Lina M.
AU - Carrasco-Portugal, Miriam del C.
AU - Flores-Murrieta, Francisco J.
AU - Vargas-Alarcón, Gilberto
AU - Aguilar-Salinas, Carlos A.
AU - Villarreal-Molina, Teresa
AU - Canizales-Quinteros, Samuel
N1 - Publisher Copyright:
© 2018 Elsevier B.V.
PY - 2019/3/15
Y1 - 2019/3/15
N2 - 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.
AB - 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.
KW - Coronary artery disease
KW - Genetics
KW - Uric acid
UR - http://www.scopus.com/inward/record.url?scp=85054440521&partnerID=8YFLogxK
U2 - 10.1016/j.ijcard.2018.09.107
DO - 10.1016/j.ijcard.2018.09.107
M3 - Artículo
C2 - 30305239
SN - 0167-5273
VL - 279
SP - 168
EP - 173
JO - International Journal of Cardiology
JF - International Journal of Cardiology
ER -