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

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dc.contributor.author Macias-Kauffer, Luis R.
dc.contributor.author Villamil-Ramírez, Hugo
dc.contributor.author León-Mimila, Paola
dc.contributor.author Jacobo-Albavera, Leonor
dc.contributor.author Posadas-Romero, Carlos
dc.contributor.author Posadas-Sánchez, Rosalinda
dc.contributor.author López-Contreras, Blanca E.
dc.contributor.author Morán-Ramos, Sofía
dc.contributor.author Romero-Hidalgo, Sandra
dc.contributor.author Acuña-Alonzo, Víctor
dc.contributor.author Del-Río-Navarro, Blanca E.
dc.contributor.author Bortolini, Maria-Cátira
dc.contributor.author Gallo López-Aliaga, Carla Maria
dc.contributor.author Bedoya, Gabriel
dc.contributor.author Rothhammer, Francisco
dc.contributor.author González-Jose, Rolando
dc.contributor.author Ruiz-Linares, Andrés
dc.contributor.author Stephens, Christopher R.
dc.contributor.author Velazquez-Cruz, Rafael
dc.contributor.author Fernández Del Valle-Laisequilla, Cecilia
dc.contributor.author Reyes-García, Juan G.
dc.contributor.author Barranco Garduño, Lina M.
dc.contributor.author Carrasco-Portugal, Miriam Del C.
dc.contributor.author Flores-Murrieta, Francisco J.
dc.contributor.author Vargas-Alarcón, Gilberto
dc.contributor.author Aguilar-Salinas, Carlos A.
dc.contributor.author Villarreal-Molina, Teresa
dc.contributor.author Canizales-Quinteros, Samuel
dc.date.accessioned 2018-11-30T03:10:47Z
dc.date.available 2018-11-30T03:10:47Z
dc.date.issued 2018
dc.identifier.uri https://hdl.handle.net/20.500.12866/4077
dc.description.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. en_US
dc.language.iso eng
dc.publisher Elsevier
dc.relation.ispartofseries International Journal of Cardiology
dc.rights info:eu-repo/semantics/restrictedAccess
dc.rights.uri https://creativecommons.org/licenses/by-nc-nd/4.0/deed.es
dc.subject ABCG2 gene en_US
dc.subject adult en_US
dc.subject aged en_US
dc.subject Article en_US
dc.subject breast cancer resistance protein en_US
dc.subject child en_US
dc.subject cohort analysis en_US
dc.subject controlled study en_US
dc.subject coronary artery disease en_US
dc.subject Coronary artery disease en_US
dc.subject estimated glomerular filtration rate en_US
dc.subject female en_US
dc.subject gender en_US
dc.subject gene en_US
dc.subject gene locus en_US
dc.subject genetic variability en_US
dc.subject Genetics en_US
dc.subject genome-wide association study en_US
dc.subject genotype en_US
dc.subject human en_US
dc.subject major clinical study en_US
dc.subject male en_US
dc.subject Mendelian randomization analysis en_US
dc.subject metabolic syndrome X en_US
dc.subject Mexican en_US
dc.subject Mexico en_US
dc.subject obesity en_US
dc.subject priority journal en_US
dc.subject single nucleotide polymorphism en_US
dc.subject SLC2A9 gene en_US
dc.subject uric acid en_US
dc.subject Uric acid en_US
dc.subject uric acid blood level en_US
dc.title Genetic contributors to serum uric acid levels in Mexicans and their effect on premature coronary artery disease en_US
dc.type info:eu-repo/semantics/article
dc.identifier.doi https://doi.org/10.1016/j.ijcard.2018.09.107
dc.subject.ocde https://purl.org/pe-repo/ocde/ford#3.02.04
dc.relation.issn 1874-1754


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