A study of Icelanders has revealed that the loss of 12 letters of genetic code in a single gene substantially reduces the risk for a heart attack and also lowers cholesterol levels. Heart attacks happen when the flow of oxygen rich blood through a coronary artery to a region of the heart muscle is blocked. Without blood flow, the muscle in the deprived region of the heart will begin to die and is replaced by scar tissue resulting in permanent damage to the heart.
The most common cause of heart attacks is coronary heart disease or CHD in which there is accumulation of a waxy substance in arteries leading to a plaque. This accumulation can progress for years resulting in a condition called atherosclerosis. When plaques get big enough to block the artery, this is called ischemia. Plaques can also rupture leading to the formation of a blood clot. If the clot gets large enough, it can completely block the flow of blood.
The most common risk factors for CHD are high LDL cholesterol, low HDL cholesterol, high blood pressure, family history, diabetes and smoking.
A heart attack can also result from a severe spasm of a coronary artery, which also blocks the flow of blood to a region of the heart. This cause of a heart attack is less common than CHD. Some 17.3 million people die of heart disease every year, making it the number one cause of death worldwide.
In the analysis of the genomes of 2,636 Icelanders, a gene called ASGR1 on chromosome 17 was found to lack 12 letters of the genetic code. This type of mutation is called a deletion. Those with this ASGR1 mutation reduced their risk of heart disease and stroke by a whopping 34 percent.
The ASGR1 gene normally produces a part of the asialoglycoprotein receptor that maintains the proper levels of molecules called glycoproteins in the blood. However, the mutated ASGR1 protein cannot do this. It is not clear how this mutation leads to a reduction in LDL-cholesterol or bad cholesterol. Scientists think that this might increase the LDL-cholesterol receptors in the liver thereby reducing circulating levels of bad cholesterol in blood. However, it is not clear what other effects of this mutation contribute to the reduction in CHD. Researchers are designing drugs that would target the ASGR1 protein and hope to be in human testing in 2 years.
Genome sequencing has also revealed that patients with very low cholesterol levels and dramatically reduced risks of heart attack had mutations in another gene called PCSK9. That has already lead to the development of other drugs, Repatha, Regeneron and Praluent. Overall, there are six other genes where genetic changes reduce heart disease risk by altering proteins involved with cholesterol and other fats in blood.
The dramatic reduction in the cost and speed at which human genomes can now be sequenced is dramatically changing the way we identify causes of diseases, pointing to new avenues for treatment and guiding the most appropriate treatment for each person. This is the goal of precision medicine. The world-wide sharing of genomic information will accelerate this process but also poses potential risks to privacy of our genetic information.