Juha Kere

When a young, well-trained person in their 30s or 40s is removed from a heart attack, it almost always comes as a big shock to the environment. Hereditary blood fat disorders are often the cause of so young people suffering from cardiovascular disease. It is estimated that about 2 percent of the population has elevated levels of the most common blood fats cholesterol and triglycerides because of its genetic inheritance. But most people are not aware of it, says Bo Angelin, professor of clinical metabolism at Karolinska Institutet. - Despite high cholesterol levels, there may be no symptoms of illness. In addition, you may not know that there are heart diseases in the genus, and even if you know it, you don't always think it can affect yourself. Therefore, in order to be able to develop earlier diagnostics and treatment, more knowledge about the disease mechanisms at the molecular level is needed, especially in order to identify and treat people who have no symptoms of elevated blood fats. Genetic patterns behind the disease Bo Angelin came up with the topic in her doctoral dissertation in the 1970s. Even then, scientists began to see genetic patterns behind the unusual blood fat disorders. - If you found an individual with high cholesterol levels and then went on to examine the rest of the family tree, it turned out that on average every other sibling had high values and every other normal values. The disease gene is inherited via dominant inheritance according to Mendel. Thus, it is enough with a disposition from one parent. Ideally, the researchers want to collect blood samples from everyone in the family, including the married ones, and from as many generations as possible. Occasions are inherited from both sides. One parent may have high cholesterol and the other low cholesterol. In the child, the value may look quite normal, while it is mixed differently in the grandchild. - We asked these research questions forty years ago, but then there was no technology that could give us the answers. Now we can do genetic studies of whole families both temporally and financially. The price tag for doing a sequence analysis of the DNA of the entire coding genome a few years ago was several million SEK, but is now down to a few thousand SEK per individual. Early detection saves lives At most, Bo Angelin and his colleagues have investigated 16 members from the same family. Those who are identified as high-risk patients can be treated with modern drugs, such as cholesterol-lowering statins, thus eliminating the risk of early disease. Patients benefit from getting the information as quickly as possible. - People think it's good to know about risk patterns. If dad has had a heart attack early then it is a high pressure to investigate the children. Even in hereditary diseases where there is no cure, most people still want to know how it is. Bo Angelin says that it is not uncommon for some patients to be interested in delving into their genealogy and to start genealogy. - I've had to follow families for several generations myself. In 1974, I traveled to Åland to investigate a family, and now I have met the grandchild of a patient I met then. His mother was not even born at the time we tested his grandfather. Mapping of rare mutations To date, the researchers have mapped a number of different disease genes and many more mutations in these genes. There can be as many as 1,700 different mutations in one gene, and each mutation is specific to a genus. This in turn means that each family is unique. - We put a lot of energy into characterizing the different mutations using different techniques, but also through clinical observations. In some families, you see skin changes, such as yellow cholesterol deposits in the skin. The researchers are trying to identify rare and distinct phenotypes, that is, the entire overall picture of the genetic and visible traits. In the next step, they can begin to assume that all individuals with that image should have a specific mutation in a specific gene. Detective work goes on. Eventually, researchers discover another genus that has a similar phenotype, and finds a previously unknown mutation in the same gene. Thus, the mapping can continue on a larger scale. By combining families and families with a similar image and looking for rare mutations, one can also begin to discover and understand new mechanisms, according to Bo Angelin. - A mutation can be likened to nature's own knockout attempt. It is a powerful tool to understand more about the mechanisms behind the disease. And when you understand the mechanisms, you also get inputs to test new therapies that can be useful not only for these families, but also for larger patient groups with cardiovascular disease. Text Nils Johan Tjärnlund Pictures Magnus Bergström Published: 2014