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Exome Sequencing Data Analysis and a Case-Control Study in Mexican Population Reveals Lipid Trait Associations of New and Known Genetic Variants in Dyslipidemia-Associated Loci.
Jurado-Camacho, Pedro A; Cid-Soto, Miguel A; Barajas-Olmos, Francisco; García-Ortíz, Humberto; Baca-Peynado, Paulina; Martínez-Hernández, Angélica; Centeno-Cruz, Federico; Contreras-Cubas, Cecilia; González-Villalpando, María Elena; Saldaña-Álvarez, Yolanda; Salas-Martinez, Guadalupe; Mendoza-Caamal, Elvia C; González-Villalpando, Clicerio; Córdova, Emilio J; Orozco, Lorena.
Afiliación
  • Jurado-Camacho PA; Immunogenomics and Metabolic Diseases Laboratory, National Institute of Genomic Medicine, Mexico City, Mexico.
  • Cid-Soto MA; Posgraduate in Biomedical Sciences, National Autonomous University of Mexico, Mexico City, Mexico.
  • Barajas-Olmos F; Immunogenomics and Metabolic Diseases Laboratory, National Institute of Genomic Medicine, Mexico City, Mexico.
  • García-Ortíz H; Immunogenomics and Metabolic Diseases Laboratory, National Institute of Genomic Medicine, Mexico City, Mexico.
  • Baca-Peynado P; Immunogenomics and Metabolic Diseases Laboratory, National Institute of Genomic Medicine, Mexico City, Mexico.
  • Martínez-Hernández A; Immunogenomics and Metabolic Diseases Laboratory, National Institute of Genomic Medicine, Mexico City, Mexico.
  • Centeno-Cruz F; Posgraduate in Biomedical Sciences, National Autonomous University of Mexico, Mexico City, Mexico.
  • Contreras-Cubas C; Immunogenomics and Metabolic Diseases Laboratory, National Institute of Genomic Medicine, Mexico City, Mexico.
  • González-Villalpando ME; Immunogenomics and Metabolic Diseases Laboratory, National Institute of Genomic Medicine, Mexico City, Mexico.
  • Saldaña-Álvarez Y; Immunogenomics and Metabolic Diseases Laboratory, National Institute of Genomic Medicine, Mexico City, Mexico.
  • Salas-Martinez G; Centro de Estudios en Diabetes, Unidad de Investigación en Diabetes y Riesgo Cardiovascular, Centro de Investigación en Salud Poblacional, Instituto Nacional de Salud Pública, Mexico City, Mexico.
  • Mendoza-Caamal EC; Immunogenomics and Metabolic Diseases Laboratory, National Institute of Genomic Medicine, Mexico City, Mexico.
  • González-Villalpando C; Immunogenomics and Metabolic Diseases Laboratory, National Institute of Genomic Medicine, Mexico City, Mexico.
  • Córdova EJ; Clinical Area, National Institute of Genomic Medicine, Mexico City, Mexico.
  • Orozco L; Centro de Estudios en Diabetes, Unidad de Investigación en Diabetes y Riesgo Cardiovascular, Centro de Investigación en Salud Poblacional, Instituto Nacional de Salud Pública, Mexico City, Mexico.
Front Genet ; 13: 807381, 2022.
Article en En | MEDLINE | ID: mdl-35669185
Background: Plasma lipid levels are a major risk factor for cardiovascular diseases. Although international efforts have identified a group of loci associated with the risk of dyslipidemia, Latin American populations have been underrepresented in these studies. Objective: To know the genetic variation occurring in lipid-related loci in the Mexican population and its association with dyslipidemia. Methods: We searched for single-nucleotide variants in 177 lipid candidate genes using previously published exome sequencing data from 2838 Mexican individuals belonging to three different cohorts. With the extracted variants, we performed a case-control study. Logistic regression and quantitative trait analyses were implemented in PLINK software. We used an LD pruning using a 50-kb sliding window size, a 5-kb window step size and a r2 threshold of 0.1. Results: Among the 34251 biallelic variants identified in our sample population, 33% showed low frequency. For case-control study, we selected 2521 variants based on a minor allele frequency ≥1% in all datasets. We found 19 variants in 9 genes significantly associated with at least one lipid trait, with the most significant associations found in the APOA1/C3/A4/A5-ZPR1-BUD13 gene cluster on chromosome 11. Notably, all 11 variants associated with hypertriglyceridemia were within this cluster; whereas variants associated with hypercholesterolemia were located at chromosome 2 and 19, and for low high density lipoprotein cholesterol were in chromosomes 9, 11, and 19. No significant associated variants were found for low density lipoprotein. We found several novel variants associated with different lipemic traits: rs3825041 in BUD13 with hypertriglyceridemia, rs7252453 in CILP2 with decreased risk to hypercholesterolemia and rs11076176 in CETP with increased risk to low high density lipoprotein cholesterol. Conclusions: We identified novel variants in lipid-regulation candidate genes in the Mexican population, an underrepresented population in genomic studies, demonstrating the necessity of more genomic studies on multi-ethnic populations to gain a deeper understanding of the genetic structure of the lipemic traits.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Tipo de estudio: Observational_studies / Prognostic_studies / Risk_factors_studies País/Región como asunto: Mexico Idioma: En Revista: Front Genet Año: 2022 Tipo del documento: Article País de afiliación: México Pais de publicación: Suiza

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Tipo de estudio: Observational_studies / Prognostic_studies / Risk_factors_studies País/Región como asunto: Mexico Idioma: En Revista: Front Genet Año: 2022 Tipo del documento: Article País de afiliación: México Pais de publicación: Suiza