Rare gene mutation protects people from ‘bad’ cholesterol

Isn’t it odd how certain people can eat junk food and smoke for most of their adult lives and never have cholesterol or heart problems? Seems almost unfair. In most people, poor diets, smoking, and a family history of high cholesterol dooms them to a lifetime of watching what they eat and taking drugs to lower their cholesterol. High levels of bad cholesterol (also called LDL) is associated with an increased risk of developing atherosclerosis (hardening and narrowing of the arteries). Alternatively, high levels of good cholesterol (or HDL) are associated with protection from atherosclerosis and heart disease. When patients have elevated levels of LDL, they are often given drugs like statins to try and bring those under control. What we don’t completely understand is why certain people are more or less susceptible to having dysfunctional cholesterol levels and therefore atherosclerosis and heart disease. A group of researchers from Iceland publishing in the New England Journal of Medicine studied the genome of 119,000 people from Icelandic decent in hopes of finding variations that may contribute to dysfunctional cholesterol levels. What they stumbled across was a variation in a gene that may one day be able to help treat high cholesterol and prevent heart disease.

The researchers found a variant in a gene called Asialoglycoprotein receptor 1 (or ASGR1) that was associated with significantly lower levels of non-HDL cholesterol (or all cholesterol that isn’t good cholesterol). Specifically, this variant was able to lower the non-HDL cholesterol on average by 0.40mmol/L. This is enough to move someone’s non-HDL levels from being high to ideal. In addition, the researchers saw that people with this mutation had a 34% lower risk of coronary artery disease or heart disease. Now it is important to note that this is a relatively rare mutation, less than 0.5% of all the people tested in this population had the variant and the researchers only tested people from Iceland, Denmark, and the Netherlands. This means that more work is needed to determine if this mutation is found in populations outside of the Nordic countries. It also means that your chance of having this beneficial mutation is low. However, this mutation offers a potential therapeutic target for people who have a family history of high cholesterol or heart disease. Since the mutation identified here causes a loss in the normal function of the protein then we could develop a drug to this protein to mimic the loss of function.

It is interesting to note that the mutation also is associated with increased levels of vitamin B12, although we don’t know yet if this has anything to do with the protection against heart disease. Much more work is needed to confirm the role of this protein in balancing cholesterol levels in the blood but it promises to help scientists understand how the body deals with cholesterol and promises to help patients control their cholesterol and their risk for heart disease.

Photo credit: Juhan Sonin Flickr


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