ArticleArteriosclerosis, thrombosis, and vascular biology2015
Myocardial Infarction-Associated SNP at 6p24 Interferes With MEF2 Binding and Associates With PHACTR1 Expression Levels in Human Coronary Arteries.
Article in Arteriosclerosis, thrombosis, and vascular biology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers, 2 of them syntheses that pooled it.
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Who cites it
54 citing papers in PubMed, 2 syntheses or guidelines pooled it, 89 citations in OpenAlex.
- The landscape of GWAS validation; systematic review identifying 309 validated non-coding variants across 130 human diseases.BMC medical genomics · 2022Pooled it
- Genetic Polymorphism of Matrix Metalloproteinase-9 and Susceptibility to Myocardial Infarction: A Meta-Analysis.Disease markers · 2022Pooled it
- Risk Haplotype of BTNL2 Predisposes Male Patients to NSTEMI: A Genetic and Functional Study.Research square · 2026Article
- Multi-omic analysis of human PHACTR1 signaling networks.Communications biology · 2026Article
- Global Evaluation of Congenital Heart Disease-Associated Non-Coding Variants.Research square · 2026Article
- GWAS for Defining the Pathogenesis of Hypertension: Have They Delivered?Hypertension (Dallas, Tex. : 1979) · 2025Review
- Headaches attributed to cranial and cervical artery dissections.The journal of headache and pain · 2025Review
- Leveraging large-scale multi-omics evidences to identify therapeutic targets from genome-wide association studies.BMC genomics · 2024Article
- Article
- From Atherosclerosis to Spontaneous Coronary Artery Dissection: Defining a Clinical and Genetic Risk Spectrum for Myocardial Infarction.Current atherosclerosis reports · 2024Review
- Advancements in the Genetics of Spontaneous Coronary Artery Dissection.Current cardiology reports · 2023Review
- PHACTR1 and Atherosclerosis: It's Complicated.Arteriosclerosis, thrombosis, and vascular biology · 2023Article
- Endothelial PHACTR1 Promotes Endothelial Activation and Atherosclerosis by Repressing PPARγ Activity Under Disturbed Flow in Mice.Arteriosclerosis, thrombosis, and vascular biology · 2023Article
- PHACTR1 modulates vascular compliance but not endothelial function: a translational study.Cardiovascular research · 2023Article
- Disease-associated non-coding variants alter NKX2-5 DNA-binding affinity.Biochimica et biophysica acta. Gene regulatory mechanisms · 2023Article
- Genetics of spontaneous cervical and coronary artery dissections.Frontiers in global women's health · 2023Review
- Genome-wide associations of aortic distensibility suggest causality for aortic aneurysms and brain white matter hyperintensities.Nature communications · 2022Article
- Single-nucleus chromatin accessibility profiling highlights regulatory mechanisms of coronary artery disease risk.Nature genetics · 2022Article
- A Study of Associations Between rs9349379 (PHACTR1), rs2891168 (CDKN2B-AS), rs11838776 (COL4A2) and rs4880 (SOD2) Polymorphic Variants and Coronary Artery Disease in Iranian Population.Biochemical genetics · 2022Article
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14 authors at 1 institution in 2 countries.
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Abstract
objectiveCoronary artery disease (CAD), including myocardial infarction (MI), is the main cause of death in the world. Genome-wide association studies have identified dozens of single nucleotide polymorphisms (SNPs) associated with CAD/MI. One of the most robust CAD/MI genetic associations is with intronic SNPs in the gene PHACTR1 on chromosome 6p24. How these PHACTR1 SNPs influence CAD/MI risk, and whether PHACTR1 itself is the causal gene at the locus, is currently unknown. APPROACH AND
resultsUsing genetic fine-mapping and DNA resequencing experiments, we prioritized an intronic SNP (rs9349379) in PHACTR1 as causal variant. We showed that this variant is an expression quantitative trait locus for PHACTR1 expression in human coronary arteries. Experiments in endothelial cell extracts confirmed that alleles at rs9349379 are differentially bound by the transcription factors myocyte enhancer factor-2. We engineered a deletion of this myocyte enhancer factor-2-binding site using CRISPR/Cas9 genome-editing methodology. Heterozygous endothelial cells carrying this deletion express 35% less PHACTR1. Finally, we found no evidence that PHACTR1 expression levels are induced when stimulating human endothelial cells with vascular endothelial growth factor, tumor necrosis factor-α, or shear stress.
conclusionsOur results establish a link between intronic SNPs in PHACTR1, myocyte enhancer factor-2 binding, and transcriptional functions at the locus, PHACTR1 expression levels in coronary arteries and CAD/MI risk. Because PHACTR1 SNPs are not associated with the traditional risk factors for CAD/MI (eg, blood lipids or pressure, diabetes mellitus), our results suggest that PHACTR1 may influence CAD/MI risk through as yet unknown mechanisms in the vascular endothelium.
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