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Approved Research

Gene-centered association of a high density SNP panel of the MEF2A gene with Cardiovascular disease.

Principal Investigator: Professor Davide Noto
Approved Research ID: 79715
Approval date: March 31st 2022

Lay summary

The aim of this study is to interrogate UK Biobank databank, by extracting genetic data of the Myocyte Enhancer Factor 2A (MEF2A) gene and try understand if small genietc variations of the gene do associate with the features of the cardiovascular disease filed in the databank. In other words the study tries to understand if people with modifications of the MEF2A gene are prone or protected regarding the development of the cardiovascular disease ( e.g. myocardial infarction ).

The scientific rationale is based on the results of different studies demonstrating that a group of genes, collected under the MEF2 gene family, are able to regulate the health of human arteries, with modulating the activities of the endothelial cells, that are the cells coating the internal surface of the arteries. MEF2 genes exert several effects also on muscle cell also localized within human arteries. The activation of the MEF2A genes in the cells are know to modulate different molecular pathways that exert a protective effect on vascular cells.  Taken together, these studies support the idea that the activation of the MEF2 genes confers protection against the atherosclerotic degeneration of the arteries' walls. These studies then suggest that genetic mutations in the MEF2A gene, able to reduce the gene functionality, might be associated with an increased risk of cardiovascular disease.

The initial estimate of the project duration is 12 months, unless additional data will be required. The identification of MEF2A as a possible determinant of cardiovascular disease and coronary artery disease might open the field for novel therapeutic strategies in the treatment of such conditions.  In recent times many companies have developed therapeutic strategies able to delivery engineered genetic products within the human tissues,  and if the present  study will confirm that MEF2A is associated with atherosclerosis, a targeted delivery of a modified version of the MEF2A gene within the arterial cells might represent a future therapeutic option able to revert atherosclerosis in subject with occluded arteries, or at least to prevent future cardiovascular events.

Scope extension:

Coronary artery disease (CAD) is the first cause of death in the Western Countries. CAD is considered related to overlapping actions of several risk factors. Nevertheless, in some cases CAD seems to be inherited as a genetic disease. In one family affectd by CAD, a gene variant of the MEF2A gene seemed causative of the disease. Nevertheless, following studies on more frequent variants of the same gene failed to associate to CAD in more than 2000 subjects analyzed. The association of MEF2A genetic variations with CAD then remains an open question. The aim of this study is to access to the large UK Biobank data, extract all the variants coded for the MEF2A gene and evaluate if one or a block of variants of MEF2A result associated to CAD. The high dimensionality of the patients' database and of the panel of SNP of the biobank might help to answer the question.

New scope

Together with MEF2A, other genes might be related to CAD with mechanisms that have to be discovered. Such genes might be also investigated in terms of association with CAD by performing a genome wide association study using the UK Biobank database and the repository of gene variants, (single nucleotype polymorphisms , SNP), excluding those genes related to the common risk factors. The methodology of correcting the results of the study for the common risk factor is available in the Research Analysis Platform (RAP). More, the function of the identified genes can be investigated using the large database of phenotypic data (clinical and biochemical) in carriers of the one or two copies of the gene variants (SNP) under investigation.