Genetic contributors to serum uric acid levels in Mexicans and their effect on premature coronary artery disease
Por:
Macias-Kauffer, Luis R., Villamil-Ramirez, Hugo, Leon-Mimila, Paola, Jacobo-Albavera, Leonor, Posadas-Romero, Carlos, Posadas-Sanchez, Rosalinda, Lopez-Contreras, Blanca E., Moran-Ramos, Sofia, Romero-Hidalgo, Sandra, Acuña-Alonzo V., del-Rio-Navarro, Blanca E., Bortolini M.-C., Gallo, Carla, Bedoya, Gabriel, Rothhammer, Francisco, Gonzalez-Jose, Rolando, Ruiz-Linares, Andres, Stephens, Christopher R., Velazquez-Cruz, Rafael, Fernandez del Valle-Laisequilla, Cecilia, Reyes-Garcia, Juan G., Barranco Garduño L.M., Carrasco-Portugal M.D.C., Flores-Murrieta, Francisco J., Vargas-Alarcon, Gilberto, Aguilar-Salinas C.A., Villarreal-Molina, Teresa, Canizales-Quinteros, Samuel
Publicada:
15 mar 2019
Ahead of Print:
1 ene 2018
Categoría:
Cardiology and cardiovascular medicine
Resumen:
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 (ß = -0.47 mg/dl, P = 1.57 × 10-42 for lead SNP rs7678287) and ABCG2 (ß = 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. © 2018 Elsevier B.V.
Filiaciones:
Macias-Kauffer, Luis R.:
Programa de Maestría y Doctorado en Ciencias Médicas, Odontológicas y de la Salud, Universidad Nacional Autónoma de México (UNAM), Mexico City, Mexico
Unidad de Genómica de Poblaciones Aplicada a la Salud, Facultad de Química, UNAM/Instituto Nacional de Medicina Genómica (INMEGEN), Mexico City, Mexico
Univ Nacl Autonoma Mexico, Programa Maestria & Doctorado Ciencias Med Odonto, Mexico City, DF, Mexico
Univ Nacl Autonoma Mexico, Inst Natl Med Genom INMEGEN, Fac Quim, Unidad Genom Poblac Aplicada Salud, Mexico City, DF, Mexico
Villamil-Ramirez, Hugo:
Unidad de Genómica de Poblaciones Aplicada a la Salud, Facultad de Química, UNAM/Instituto Nacional de Medicina Genómica (INMEGEN), Mexico City, Mexico
Univ Nacl Autonoma Mexico, Inst Natl Med Genom INMEGEN, Fac Quim, Unidad Genom Poblac Aplicada Salud, Mexico City, DF, Mexico
Leon-Mimila, Paola:
Unidad de Genómica de Poblaciones Aplicada a la Salud, Facultad de Química, UNAM/Instituto Nacional de Medicina Genómica (INMEGEN), Mexico City, Mexico
Univ Nacl Autonoma Mexico, Inst Natl Med Genom INMEGEN, Fac Quim, Unidad Genom Poblac Aplicada Salud, Mexico City, DF, Mexico
Jacobo-Albavera, Leonor:
Laboratorio de Enfermedades Cardiovasculares, INMEGEN, Mexico City, Mexico
INMEGEN, Lab Enfermedades Cardiovasc, Mexico City, DF, Mexico
Posadas-Romero, Carlos:
Departamento de Endocrinología, Instituto Nacional de Cardiología Ignacio Chávez, Mexico City, Mexico
Inst Nacl Cardiol Ignacio Chavez, Dept Endocrinol, Mexico City, DF, Mexico
Posadas-Sanchez, Rosalinda:
Departamento de Endocrinología, Instituto Nacional de Cardiología Ignacio Chávez, Mexico City, Mexico
Inst Nacl Cardiol Ignacio Chavez, Dept Endocrinol, Mexico City, DF, Mexico
Lopez-Contreras, Blanca E.:
Unidad de Genómica de Poblaciones Aplicada a la Salud, Facultad de Química, UNAM/Instituto Nacional de Medicina Genómica (INMEGEN), Mexico City, Mexico
Univ Nacl Autonoma Mexico, Inst Natl Med Genom INMEGEN, Fac Quim, Unidad Genom Poblac Aplicada Salud, Mexico City, DF, Mexico
Moran-Ramos, Sofia:
Unidad de Genómica de Poblaciones Aplicada a la Salud, Facultad de Química, UNAM/Instituto Nacional de Medicina Genómica (INMEGEN), Mexico City, Mexico
Univ Nacl Autonoma Mexico, Inst Natl Med Genom INMEGEN, Fac Quim, Unidad Genom Poblac Aplicada Salud, Mexico City, DF, Mexico
Romero-Hidalgo, Sandra:
Departamento de Genómica Computacional, INMEGEN, Mexico City, Mexico
INMEGEN, Dept Genom Computat, Mexico City, DF, Mexico
Acuña-Alonzo V.:
Escuela Nacional de Antropología e Historia, Mexico City, Mexico, UCL Genetics Institute, University College London, London, WC1E 6BT, United Kingdom
del-Rio-Navarro, Blanca E.:
Hospital Infantil de México Federico Gómez, Mexico City, 06720, Mexico
Hosp Infantil Mexico Dr Federico Gomez, Mexico City 06720, DF, Mexico
Bortolini M.-C.:
Departamento de Genética, Universidade Federal do Rio Grande do Sul, Porto Alegre, 91501-970, Brazil
Gallo, Carla:
Laboratorios de Investigación y Desarrollo, Facultad de Ciencias y Filosofía, Universidad Peruana Cayetano Heredia, Lima, 31, Peru
Univ Peruana Cayetano Heredia, Fac Ciencias & Filosofia, Lab Invest & Desarrollo, Lima 31, Peru
Bedoya, Gabriel:
GENMOL (Genética Molecular), Universidad de Antioquia, Medellín, 5001000, Colombia
Univ Antioquia, GENMOL Genet Mol, Medellin 5001000, Colombia
Rothhammer, Francisco:
Instituto de Alta Investigación, Universidad de Tarapacá e ICBM Facultad de Medicina Universidad de Chile1000009, Chile
Univ Tarapaca, Inst Alta Invest, Arica, Chile
Univ Chile, ICBM, Fac Med, Santiago 1000009, Chile
Gonzalez-Jose, Rolando:
Instituto Patagónico de Ciencias Sociales y Humanas (CENPAT-CONICET), Puerto Madryn, U9120ACD, Argentina
Consejo Nacl Invest Cient & Tecn, Inst Patagon Ciencias Sociales & Humans CENPAT, U9120ACD, Puerto Madryn, Argentina
Ruiz-Linares, Andres:
Ministry of Education Key Laboratory of Contemporary Anthropology and Collaborative Innovation Center of Genetics and Development, School of Life Sciences and Human Phenome Institute, Fudan University, Shanghai, China
Aix-Marseille Univ, CNRS, EFS, ADES, Marseille, France
Fudan Univ, Minist Educ, Key Lab Contemporary Anthropol, Shanghai, Peoples R China
Fudan Univ, Sch Life Sci, Collaborat Innovat Ctr Genet & Dev, Shanghai, Peoples R China
Fudan Univ, Human Phenome Inst, Shanghai, Peoples R China
Aix Marseille Univ, CNRS, FES, ADES, Marseille, France
Stephens, Christopher R.:
C3-Centro de Ciencias de la Complejidad e Instituto de Ciencias Nucleares, UNAM, Ciudad de México, Mexico
UNAM, C3, Ciudad De Mexico, Mexico
UNAM, Inst Ciencias Nucl, Ciudad De Mexico, Mexico
Velazquez-Cruz, Rafael:
Laboratorio de Genómica del Metabolismo Óseo, Instituto Nacional de Medicina Genómica (INMEGEN), Mexico City, Mexico
Inst Nacl Med Genom INMEGEN, Lab Genom Metab Oseo, Mexico City, DF, Mexico
Fernandez del Valle-Laisequilla, Cecilia:
Investigación Clínica y Farmacovigilancia, Productos Medix, S.A. de C.V., Mexico City, Mexico
Prod Medix SA CV, Invest Clin & Farmacovigilancia, Mexico City, DF, Mexico
Reyes-Garcia, Juan G.:
Sección de Estudios de Posgrado e Investigacion, Escuela Superior de Medicina, Instituto Politécnico Nacional, Mexico City, Mexico
Inst Politecn Nacl, Escuela Super Med, Sect Estudios Posgrad & Invest, Mexico City, DF, Mexico
Barranco Garduño L.M.:
Unidad de Investigación en Farmacología, Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas, Mexico City, Mexico
Carrasco-Portugal M.D.C.:
Unidad de Investigación en Farmacología, Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas, Mexico City, Mexico
Flores-Murrieta, Francisco J.:
Sección de Estudios de Posgrado e Investigacion, Escuela Superior de Medicina, Instituto Politécnico Nacional, Mexico City, Mexico
Unidad de Investigación en Farmacología, Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas, Mexico City, Mexico
Inst Politecn Nacl, Escuela Super Med, Sect Estudios Posgrad & Invest, Mexico City, DF, Mexico
Inst Nacl Enfermedades Resp Ismael Cosio Villegas, Unidad Invest & Farmacol, Mexico City, DF, Mexico
Vargas-Alarcon, Gilberto:
Departamento de Biología Molecular, Instituto Nacional de Cardiología Ignacio Chávez, México City, Mexico
Inst Nacl Cardiol Ignacio Chavez, Dept Biol Mol, Mexico City, DF, Mexico
Aguilar-Salinas C.A.:
Unidad de Investigación en Enfermedades Metabólicas and Departamento de Endocrinología y Metabolismo, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
Tecnológico de Monterrey, Escuela de Medicina y Ciencias de la Salud. Monterrey, N.L., Mexico
Tecnológico de Monterrey, Escuela de Medicina y Ciencias de la Salud., Monterrey, N.L., Mexico
Villarreal-Molina, Teresa:
Laboratorio de Enfermedades Cardiovasculares, INMEGEN, Mexico City, Mexico
INMEGEN, Lab Enfermedades Cardiovasc, Mexico City, DF, Mexico
Canizales-Quinteros, Samuel:
Unidad de Genómica de Poblaciones Aplicada a la Salud, Facultad de Química, UNAM/Instituto Nacional de Medicina Genómica (INMEGEN), Mexico City, Mexico
Univ Nacl Autonoma Mexico, Inst Natl Med Genom INMEGEN, Fac Quim, Unidad Genom Poblac Aplicada Salud, Mexico City, DF, Mexico
Inst Natl Ciencias Med & Nutr Salvador Zubiran, Unidad Invest Enfermedades Metabol, Mexico City, DF, Mexico
Inst Natl Ciencias Med & Nutr Salvador Zubiran, Dept Endocrinol & Metab, Mexico City, DF, Mexico
Tecnol Monterrey, Escuela Med & Ciencias Salud, Monterrey, NL, Mexico
Escuela Nacl Antropol & Hist, Mexico City, DF, Mexico
UCL, UCL Genet Inst, London WC1E 6BT, England
Univ Fed Rio Grande do Sul, Dept Genet, BR-91501970 Porto Alegre, RS, Brazil
|