Molecular Characterization of the Lipid Genome-Wide Association Study Signal on Chromosome 18q11.2 Implicates HNF4A-Mediated Regulation of the TMEM241 Gene
| Autor: | Rodríguez, Alejandra, Gonzalez, Luis, Ko, Arthur, Alvarez, Marcus, Miao, Zong, Bhagat, Yash, Nikkola, Elina, Cruz-Bautista, Ivette, Arellano-Campos, Olimpia, Muñoz-Hernández, Linda L, Ordóñez-Sánchez, Maria-Luisa, Rodriguez-Guillen, Rosario, Mohlke, Karen L, Laakso, Markku, Tusie-Luna, Teresa, Aguilar-Salinas, Carlos A, Pajukanta, Päivi |
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| Rok vydání: | 2016 |
| Předmět: |
Genetic Markers
Male Genotype Quantitative Trait Loci Clinical Sciences Cardiorespiratory Medicine and Haematology Transfection Chromosomes Linkage Disequilibrium Genetic Genetics Humans 2.1 Biological and endogenous factors Polymorphism Aetiology dyslipidemias Reporter Mexico triglycerides Finland Aged mechanisms Pair 18 Binding Sites genome-wide association study gene expression and regulation Human Genome Membrane Proteins Single Nucleotide Hep G2 Cells Middle Aged Lipid Metabolism United States Up-Regulation Phenotype Genes Hepatocyte Nuclear Factor 4 Cardiovascular System & Hematology chromatin Digestive Diseases Transcription functional genomics Human Biotechnology |
| Zdroj: | Arteriosclerosis, thrombosis, and vascular biology, vol 36, iss 7 |
| ISSN: | 1725-9126 |
| Popis: | ObjectiveWe recently identified a locus on chromosome 18q11.2 for high serum triglycerides in Mexicans. We hypothesize that the lead genome-wide association study single-nucleotide polymorphism rs9949617, or its linkage disequilibrium proxies, regulates 1 of the 5 genes in the triglyceride-associated region.Approach and resultsWe performed a linkage disequilibrium analysis and found 9 additional variants in linkage disequilibrium (r(2)>0.7) with the lead single-nucleotide polymorphism. To select the variants for functional analyses, we annotated the 10 variants using DNase I hypersensitive sites, transcription factor and chromatin states and identified rs17259126 as the lead candidate variant for functional in vitro validation. Using luciferase transcriptional reporter assay in liver HepG2 cells, we found that the G allele exhibits a significantly lower effect on transcription (P |
| Databáze: | OpenAIRE |
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