A Single Common Genetic Variant Linked To 5 Vascular Diseases

A common genetic variant in chromosome 6p24 has been implicated by genome wide studies to be associated with coronary artery disease, cervical artery dissection, migraine headache, hypertension, and fibromuscular dysplasia. Exactly how it is that this polymorphism affects the risks for so many diseases is not clear. As published in the journal Cell, this DNA variant enhances activity of the gene called endothelin-1, which is a gene known to promote hardening of the arteries and vasoconstriction.

Genetic variants associated with increased risks for developing myocardial infarction and coronary artery disease were examined which involved using data collected from the CARDIOGRAMplusC4D consortium and the 1000 Genomes project from close to 200,000 individuals.  The researchers were focused on single nucleotide polymorphism variations that will affect a single DNA building block.  An SNP called rs9349379 was shown as being the strongest risk factor for the development of cardiovascular disease at chromosome 6p24 after analysis of the data.  In 112,338 people of European ancestry with 36% of them having G allele, a specific form of rs9349379, it was associated with the increased risk of developing coronary artery disease. DNA in small region of re9349379 in a human pluripotent stem cell was deleted using CRISPR/Cas9 gene editing, the immature cells were converted into vascular cells to investigate how rs9349379 regulates the activity of the distant EDN1 gene. Blood sample analysis from 99 healthy individuals showed G allele at re0340379 to be associated with increased levels of big endothelin-1, which is a precursor protein product of the gene EDN1.

Research conducted in the past has shown that ET-1 is the most long lasting potent vasoconstrictor in the human body, promoting development of plaques inside of the arteries, because re9349379 increases its production this genetic variant could possibly explain the co-occurrence of coronary artery disease with cervical artery dissection, hypertension, fibromuscular dysplasia, and migraine headaches. More research is needed to be conducted to explore this possibility. Further research is also needed to understand how rs9349379 is able to regulate the activity of the gene EDN1 despite the huge distance between them.

Findings from this research suggests that screening for rs9349379 may possibly improve the risk assessment for as well as strategies for the treatment and prevention of vascular diseases, and that targeting ET-1 may be beneficial in the treatment of diseases such as hypertension, coronary disease, cervical artery dissection, migraine headache, and fibromuscular dysplasia.

The risk of heart attack is determined by a combination of lifestyle choices and genetic factors, this research only identifies a single genetic risk factor, and is not a polymorphism that can predict who will and will not have a heart attack.