Which DNA changes cause cholesterol-like molecules to enter the blood?

Functional characterisation of missense variants in key genes regulating cholesterol and phytosterol absorption: Potential implications for cardiovascular health

Professor Carol Shoulders and her team at Queen Mary, University of London are identifying changes in DNA that put people at higher risk of heart and circulatory disease, and if there are ways they can lower their risk. Phytosterols are cholesterol-like substances found in many healthy foods such as broccoli, lettuce, nuts and vegetable oils. In most people phytosterols are removed from their body through the gut, where they help to prevent ‘bad’ cholesterol from being brought into the bloodstream. ABCG5/G8 is a type of protein that controls the transport of phytosterols and cholesterol. Some people have a fault in this protein, which means they can’t stop phytosterols and cholesterol from entering the bloodstream. Once in the bloodstream phytosterols are taken up by most cells including cells lining arteries, increasing the risk of heart and circulatory disease and heart attack. Professor Shoulders has found that more than 3 million people in the UK may have the rare DNA change that stops the ABCG5/G8 transporter working correctly. In this project, she will study more than 30 DNA changes to find out which ones lead to a having a faulty transporter. This research could lead to new public health advice to reduce heart and circulatory disease risk, such as avoiding foods enriched in phytosterols, or taking a drug called ezetimibe. It may also eventually identify new therapeutic ways to control ABCG5/G8 and phytosterol/cholesterol transport.