Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Gene expression and genotype in normal heart

ABSTRACT: Genome-wide association studies have identified a small region at chromosome 9p21.3 strongly associated with coronary heart disease risk. The region contains no protein-coding genes and the mechanism underlying its association with heart disease is unknown. We investigated associations between rs1333049, a single nucleotide polymorphism representing the 9p21.3 locus, and levels of cardiac gene expression in myocardial tissue from donors with no documented history of heart disease. Individual myocardial gene expression profiles were generated with Affymetrix Human Gene 1.0 ST arrays (n=108). DNA genotyping was performed with Taqman assays. Associations between genotype and gene expression were analyzed assuming a recessive effect.

ORGANISM(S): Homo sapiens

SUBMITTER: Anna Pilbrow

PROVIDER: E-GEOD-22253 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

The chromosome 9p21.3 coronary heart disease risk allele is associated with altered gene expression in normal heart and vascular tissues.

Pilbrow Anna P AP Folkersen Lasse L Pearson John F JF Brown Chris M CM McNoe Les L Wang Nancy M NM Sweet Wendy E WE Tang W H Wilson WH Black Michael A MA Troughton Richard W RW Richards A Mark AM Franco-Cereceda Anders A Gabrielsen Anders A Eriksson Per P Moravec Christine S CS Cameron Vicky A VA

PloS one 20120629 6

Genome-wide association studies have identified a coronary artery disease (CAD) risk locus in a non-coding region at 9p21.3, the nearest genes being CDKN2A and CDKN2B. To understand the pathways by which this locus might influence CAD susceptibility, we investigated associations between the 9p21.3 risk genotype and global gene expression in heart tissue from donors with no diagnosed heart disease (n = 108, predominant cause of death, cerebral vascular accident) and in carotid plaque (n = 106), a ...[more]

PMID: 22768093

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Project description:Ischemic cardiopathy is the leading cause of death in the world, for which efficient regenerative therapy is not currently available. In mammals, after a myocardial infarction episode, the damaged myocardium is replaced by scar tissue featuring collagen deposition and tissue remodelling with negligible cardiomyocyte proliferation. Zebrafish, in contrast, display an extensive regenerative capacity as they are able to restore completely lost cardiac tissue after partial ventricular amputation. Due to the lack of genetic lineage tracing evidence, it is not yet clear if new cardiomyocytes arise from existing contractile cells or from an uncharacterised set of progenitors cells. Nonetheless, several genes and molecules have been shown to participate in this process, some of them being cardiomyocyte mitogens in vitro. Though questions as what are the early signals that drive the regenerative response and what is the relative role of each cardiac cell in this process still need to be answered, the zebrafish is emerging as a very valuable tool to understand heart regeneration and devise strategies that may be of potential value to treat human cardiac disease. Here, we performed a genome-wide transcriptome profile analysis focusing on the early time points of zebrafish heart regeneration and compared our results with those of previously published data. Our analyses confirmed the differential expression of several transcripts, and identified additional genes the expression of which is differentially regulated during zebrafish heart regeneration. We validated the microarray data by conventional and/or quantitative RT-PCR. For a subset of these genes, their expression pattern was analyzed by in situ hybridization and shown to be upregulated in the regenerating area of the heart. The specific role of these new transcripts during zebrafish heart regeneration was further investigated ex vivo using primary cultures of zebrafish cardiomyocytes and/or epicardial cells. Our results offer new insights into the biology of heart regeneration in the zebrafish and, together with future experiments in mammals, may be of potential interest for clinical applications. In order to study zebrafish heart regeneration, a time course experiment was realized where amputated heart regenerating were compared to control heart. Samples in triplicate were extracted at 1, 3, 5 and 7 days post-amputation.

Dataset Information

Gene expression and genotype in normal heart

Publications

The chromosome 9p21.3 coronary heart disease risk allele is associated with altered gene expression in normal heart and vascular tissues.

Similar Datasets

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