Welcome, my name's Dr. Warrick Bishop. I'm a cardiologist, an author and a keynote speaker. I'm CEO of the Healthy Heart Network. I'm all about trying to help people live as well as possible for as long as possible. Heart disease is huge in Australia. Every 20 minutes someone suffers a heart attack. Most of these could probably have been avoided if only we knew what to do. This podcast is all about helping you understand. blood pressure, weight, cholesterol, for better health. If you enjoy this podcast, I would be honoured for a five-star review. You can share it with your family and friends. It may well save someone you love. G'day, my name is Dr. Eric Bishop. Welcome to my podcast and videocast station. As always, I really would like to say thanks for tuning in, and I hope you find what I'm sharing informative, helpful. and useful for your best health journey, well, or even just your health literacy. I'd like to talk about genetics in a very simple way. I'm not a geneticist. I'm not super-duper clever with all that stuff, but let me share it with you in a way that probably makes sense for us clinicians, the people seeing individuals and thinking about this. When we think about genetics, and I'm going to talk about cholesterol-related issues and genetics, when we think about genetics, we think about it in two main ways. We think about single genetic mutations that then have a significant impact on what we see for an individual in their lipid profile, and I'll talk about that in a sec. We also see what we call polygenic influences on what we see in the individual so monogenic polygenic monogenic means we identify one single abnormality for example an abnormal receptor for ldl cholesterol or the ldl particle i should say the ldl receptor so we see monogenic abnormality and can track that down to a very single and specific functional abnormality that then drives what we see in the patient's blood, like really high cholesterol LDL-C levels, really high cholesterol levels. Polygenic issues mean that the individual doesn't have necessarily one single abnormality that drives what we see in the blood, but lots of little abnormalities that come together and cause the problem. How could we compare that to something we see on a day-to-day basis? Well, for example, we could say, well, let's relate it to car accident for argument's sake. Let's say a monogenic cause of a car accident would be brake failure. in a brand new vehicle so everything's working well but the brakes fail are one single cause leading to an accident occurring let's take a polygenic cause for a car accident it might be brakes that are a bit rubbery not being bled properly it could be old brake pads could be bald tires could be dirty windscreen could be the windscreen wipers are not wiping the rain off the window are you getting a sense for what i'm talking about the shock absorbers may not be working properly the headlights may not be working properly multiple factors feeding into why the accident occurs so monogenic apologetic when it comes to the sort of patterns we see when we're dealing with people and their cholesterol issues or their blood lipid issues, there are four main types that we sort of see clinically. One is raised cholesterol. One is raised cholesterol and triglycerides. One is raised triglycerides of their own. And another is raised lipoprotein A. Well, how do each of these relate to monogenic and polygenic contribution? Well, Monogenic raised cholesterol is generally a deletion of one of the components related to the LDL receptor or PCSK9 protein. So you can have a single monogenic abnormality that drives marked elevations of LDL cholesterol. because it's not removed from the bloodstream properly. This monogenic abnormality is linked and called, it's linked in families, and it tends to be called, as you guessed, familial within families, hyper, hyper meaning increased cholesterol, the stuff we're talking about, emia within the blood. So monogenic abnormality of receptor handling for LDL. C or LDL particles giving rise to familial hypercholesterolemia. Polygenic elevated, polygenic elevated cholesterol doesn't tend to be quite as high, can be close, can run in families as well, doesn't seem to have the same significant. elevation as monogenic familial hypercholesterolemia doesn't often seem to have exactly the same family linkages and often doesn't seem to necessarily have exactly the same sort of risk for the individuals involved. Although we have to watch that very closely because either way, whether you end up with monogenic or polygenic raised LDL cholesterol, the impact is going to be pretty similar on your vasculature over time because of that rust, if you like. So they don't tend to have quite as high cholesterol levels. That's because everything's working, just not quite as well or the combination isn't quite as well rather than a complete default of one of the genes. When it comes to mixed dyslipidemia, mixed. lipid patterns with raised triglycerides, raised cholesterol, these tend to be polygenic. So we don't tend to find a single monogenic cause for this group. These people may also include individuals with a propensity toward diabetes. And that as well seems to have a multi or polygenic contribution that you'd seem to get from the family. When we see raised triglycerides in isolation, very high triglycerides in isolation, to such a degree that they can sludge up in the arteries and lead to problems of their own, like pancreatitis, this tends to be associated with a monogenic abnormality. Mild and moderate elevations of triglyceride tend to be associated with a mixed dyslipidemia and often associated with diabetes. but you can have really high triglyceride levels as a monogenic inherited condition. Our last group to consider are those with raised lipoprotein, little a, and we know that this is the most significant genetically... delineated risk factor for cardiovascular disease. These individuals have a clear marker, a clear monogenic process to their end result of raised lipoprotein, little a, and they have got that from their family. Well, monogenic, polygenic, raised cholesterol, mixed. raised cholesterol and raised triglycerides, raised triglycerides alone and lipoprotein little a. I hope that all makes a bit of sense to you, but it gives you an idea of how we're thinking what's going on. It certainly means in those ones where we know there's a monogenic issue that we'll be looking very closely at the families and sometimes we'll even be trying to identify the genes involved. Well, I hope... That makes a bit of sense to you. I hope you enjoyed it. Thank you so much for listening this far. If you have any queries or questions, drop us a note at drWarrickbishop.online. Until next time, I'm going to wish you the very best. I hope you live as well as possible for as long as possible. Take care and bye for now. 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