Phytosterols are lipid compounds formed in plants that are ingested with food, for example nuts or vegetable oils. In some cases, these are artificially added to various foods such as yoghurt or margarine, as they can lower cholesterol and are thus perceived as having a positive effect on our health. On the other hand, phytosterols are similar to cholesterols and can themselves be deposited in vascular walls, which may lead to atherosclerosis. In atherosclerosis, deposits form in the walls of medium-sized and large arteries, obstructing and blocking the flow of blood. The relationship between phytosterols and coronary heart disease is therefore a contentious issue in medical research.
Scientists from the Faculty of Medicine, in cooperation with other European study groups, conducted a genetic association analysis of phytosterol concentrations in the blood of nearly 10,000 subjects. Using a method to determine the influence of variable risk factors on diseases by exploiting genetic factors, the team succeeded in inferring causal relationships between phytosterols, cholesterol and coronary heart disease. “It appears that there are both direct and indirect cholesterol-mediated negative causal effects of phytosterols on the risk of coronary heart disease. The study thus makes a significant contribution to a discussion that has been controversial for many years,” said study leader Professor Markus Scholz from the Institute for Medical Informatics, Statistics and Epidemiology (IMISE) at Leipzig University, adding: “Although this does not yet allow an immediate conclusion regarding the addition of phytosterols to food, high phytosterol concentrations are a risk factor that should be taken into account.”
The researchers identified a total of seven regions in the genome that are associated with phytosterol concentrations in the blood. Of these, five are new. By means of bioinformatic analyses, the team then derived plausible candidate genes, meaning genes with biological effects in sterol metabolism. “This greatly expands our understanding of the genetic regulation of phytosterol concentrations in the blood. These genes, or their products and functions, represent potential targets for future drug development,” said Professor Scholz. The LIFE studies – LIFE-Adult and LIFE-Heart – as well as the so-called Sorbian study provided the majority of the case numbers from the Leipzig side, with 4114 blood samples. In addition, most phytosterol concentrations, 7042 in total, were measured at the Institute of Laboratory Medicine under the direction of Professor Uta Ceglarek. The biostatistical analyses and modelling were performed under the direction of Professor Scholz at the Institute for Medical Informatics, Statistics and Epidemiology.
Original publication in Nature Communications:
“Genome-wide meta-analysis of phytosterols reveals five novel loci and a detrimental effect on coronary atherosclerosis”, Doi: 10.1038/s41467-021-27706-6