We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
<italic>PHACTR1</italic> splicing isoforms and eQTLs in atherosclerosis-relevant human cells.
- Authors
Codina-Fauteux, Valérie-Anne; Beaudoin, Mélissa; Lalonde, Simon; Lo, Ken Sin; Lettre, Guillaume
- Abstract
Background: Genome-wide association studies (GWAS) have identified a variant (rs9349379) at the phosphatase and actin regulator 1 (<italic>PHACTR1</italic>) locus that is associated with coronary artery disease (CAD). The same variant is also an expression quantitative trait locus (eQTL) for <italic>PHACTR1</italic> in human coronary arteries (hCA). Here, we sought to characterize <italic>PHACTR1</italic> splicing pattern in atherosclerosis-relevant human cells. We also explored how rs9349379 modulates the expression of the different <italic>PHACTR1</italic> splicing isoforms. Methods: We combined rapid amplification of cDNA ends (RACE) with next-generation long-read DNA sequencing to discover all <italic>PHACTR1</italic> transcripts in many human tissues and cell types. We measured <italic>PHACTR1</italic> transcripts by qPCR to identify transcript-specific eQTLs. Results: We confirmed a brain-specific long transcript, a short transcript expressed in monocytes and four intermediate transcripts that are different due to alternative splicing of two in-frame exons. In contrast to a previous report, we confirmed that the PHACTR1 protein is present in vascular smooth muscle cells. In 158 hCA from our collection and the GTEx dataset, rs9349379 was only associated with the expression levels of the intermediate <italic>PHACTR1</italic> transcripts. Conclusions: Our comprehensive transcriptomic profiling of <italic>PHACTR1</italic> indicates that this gene encodes six main transcripts. Five of them are expressed in hCA, where atherosclerotic plaques develop. In this tissue, genotypes at rs9349379 are associated with the expression of the intermediate transcripts, but not the immune-specific short transcript. This result suggests that rs9349379 may in part influence CAD by modulating the expression of intermediate <italic>PHACTR1</italic> transcripts in endothelial or vascular smooth muscle cells found in hCA.
- Subjects
CORONARY arteries; GENE expression; MICRORNA; BIOINFORMATICS; POLYMERASE chain reaction
- Publication
BMC Medical Genetics, 2018, Vol 19, Issue 1, pN.PAG
- ISSN
1471-2350
- Publication type
Article
- DOI
10.1186/s12881-018-0616-7