Principal Investigator: Mr Mark Trinder
University of British Columbia – CanadaTags: 42857, featured, genetics/genotyping, hdl, hospitilization, infection, LDL, lipoproteins
Lipoproteins are commonly known as “good” and “bad” cholesterol. The function of lipoproteins is to transport lipids in the blood. But lipoproteins can also bind and remove bacterial toxins from the blood during an infection and reduce the severity of disease. Therefore, it is not surprising that patients with low levels of lipoproteins have an increased risk of developing infections responsible for life-threatening hospitalization and death.
Genetics influence the levels of lipoproteins in the blood, but it is unknown how these genes influence risk of infection. This study will use a large clinical database to investigate how genes that effect lipoproteins influence infectious disease risk. We predict that patients with genetic variations that enhance the ability of lipoproteins to remove bacterial toxins will have reduced risk of developing severe infections. In contrast, patients with genetic variations that impair the ability of lipoproteins to remove bacterial toxins will have increased risk of developing severe infections.
This study will take 1-2 years to complete and has important public health implications. Our work will provide new information on the role of lipoprotein genetics in health and disease. By demonstrating genetic contributions to infection risk, this work has the potential to highlight the use of currently available drugs for the new purpose of treating severe infections. Furthermore, this study could help identify patients that are increased risk of developing future infections or most likely to benefit from personalized treatments given their genetics.
Project extension February 2019:
RESEARCH QUESTION: Do genetic variants, including single-nucleotide polymorphisms and polygenic risk scores, in plasma lipoprotein-related genes influence risk of infections?
AIM 1: We will determine how single-nucleotide polymorphisms in the CETP and PCSK9 genes influence the risk of infectious disease-related hospitalization and mortality.
AIM 2: We will determine how genetic mutations in the LDLR, which are causative for familial hypercholesterolemia, influence the risk of infectious disease-related hospitalization and mortality.
AIM 3: We will determine how polygenic risk scores for low-density lipoprotein and high-density lipoprotein influence the risk of infectious disease-related hospitalization and mortality.
AIM 4 (NEW): To assess the potential pleiotropic effects of high-density lipoprotein on health and disease we will perform a phenome-wide association study using polygenic risk scores.
Last updated Mar 12, 2019