Researchers have identified gene variants linked to harmful fatty substances in the blood. In the future, it might prove possible to prevent cardiovascular disease by influencing the function of these genes.
Elevated blood cholesterol levels are one of the main risk factors for cardiovascular disease. In addition to cholesterol, other fatty substances in the blood, lipids and lipid surface proteins, apolipoproteins, are also associated with the development of heart disease. These lipids are influenced by both lifestyle and genetic factors, and especially rare genetic factors can have a major impact on the lipid composition in an individual's blood.
The current study opens the door to more detailed further research to assess the effects of these variants.
A study by the University of Helsinki and the Folkhälsan Research Center investigated rare genetic factors affecting blood lipid levels in people with type 1 diabetes.
– People with diabetes have a particularly high risk of heart disease, says researcher Niina Sandholm.
Niina Sandholm, researcher in the FinnDiane-study group.
There are already more than 500 million people worldwide with diabetes. So far, there are only few medications available that reduce the risk of heart disease among people with diabetes.
– Because type 1 diabetes starts at a young age, people with type 1 diabetes are also at higher risk of heart disease at a younger age than the rest of the population. Therefore, finding new ways to reduce the risk of developing the disease is of paramount importance, Sandholm continues.
The study involved exome sequencing, analyzing the protein-coding part of the DNA, of 1 054 participants in the Finnish FinnDiane study. Then the effect of the discovered gene variants on the participants' blood lipid levels was investigated.
The lipid values were analyzed for total cholesterol, LDL cholesterol, HDL cholesterol and triglycerides. In addition, apolipoproteins in particular were examined, as well as other more specific lipid measurements, 79 different lipid values in total.
The study found rare gene variants in the LIPC and APOB genes, already previously associated with lipid levels, that affect apolipoprotein levels. In addition, the researchers found variants in the RBM47-, TRMT5-, GTF3C5-, MARCHF10- and RYR3-genes, which have not previously been identified as being associated with cholesterol or other lipid levels.
– The LDL cholesterol-related finding in the GTF3C5 gene was of special interest. Here, one of the protein structure-modifying variants is 80 times more common in Finns than in other populations, Sandholm adds.
The variants of the GTF3C5-gene are also associated with heart disease, suggesting that it might be possible to contain the risk of heart disease by influencing these genes. However, not much is yet known about the function of the gene and the effect of the variants found.
– The current study opens the door to more detailed further research to assess the effects of these variants, confirms Professor Per-Henrik Groop, who founded the FinnDiane study.
Original Article: Sandholm et al., Whole-exome sequencing identifies novel protein-altering variants associated with serum apolipoprotein and lipid concentrations, Genome Medicine (2022) 14:132. https://doi.org/10.1186/s13073-022-01135-6
