Using single-cell technology, a new study sheds light on the importance of genetic risk factors and the diversity of cells involved in the development of coronary artery disease. The researchers analyzed human atherosclerotic lesions to map the chromatin accessibility of more than 7,000 cells. Chromatin accessibility is known to reflect active regions and genes in the genome. The findings were published in Research in circulation.
Human genome-wide genome association studies have identified more than 200 loci associated with coronary artery disease. More than 90% of them are found outside of genes encoding proteins, in the so-called regulatory elements of the cis, the importance of which in the pathogenesis of coronary artery disease is still unclear.
Previous research has shown that the development of coronary artery disease involves a wide variety of diseases cells and its subtypes. The study published now is the first to use single-cell technology to map the epigenetic changes of these cells. The researchers used the ATAC-seq sequencing method to discover the nuclear structure of chromatin in endothelial cells and smooth muscle cells, as well as immune system monocytes, macrophages, cells. NK / T and B, which provide a unique resource for studying the specific cell type. activity of cis regulatory elements in the vessel wall affected by the disease.
The study showed that variants of genetic risk associated with coronary artery disease are particularly enriched in cis-specific endothelial regulatory elements and smooth muscle cells, which indicates that these cells play an important role in the transmission of susceptibility to disease. Based on chromatin accessibility mapping and gene expression data, the researchers were able to identify target genes assumed by approximately 30% of all known loci associated with coronary artery disease. In addition, the researchers performed a fine-grained experimental mapping across the genome of the variants, which allowed them to identify potential single-nucleotide causal polymorphisms and the associated target gene for more than 30 disease-related loci. coronary artery. The study also presented a number of examples of how chromatin accessibility and gene expression data can be used to predict target cells through which the function of genetic changes associated with disease is transmitted to tissue. . This is an important step forward that helps to understand the real functional significance of risk variants in the pathophysiology of the coronary artery. disease. In the future, this information may be used to develop more effective, safer, and more individualized treatments coronary artery disease.
Tiit Örd et al, Monocellular epigenomics and functional mapping of atherosclerosis GWAS Loci, Research in circulation (2021). DOI: 10.1161 / CIRCRESAHA.121.318971
University of Eastern Finland
Citation: Cell-type-specific view on the role of risk factors in coronary artery disease (2021, July 8) retrieved July 8, 2021 at https://medicalxpress.com/news/2021 -07-cell-type-specific-insight- function-factors-coronary.html
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