The changes of lipids, lipoproteins and apolipoproteins during inflammation and infections are part of the immune response and might play an important role in protecting the host. Only few long-term prospective cohort studies exist. There is evidence that the risk for infections and/or sepsis increases with lower total and HDL cholesterol concentrations and that a reduction of CETP concentrations during a sepsis is associated with mortality. Especially HDL cholesterol and proteins associated with HDL particles such as apolipoprotein A-IV seem to play an important role in infections. Thus the hypothesis for this project is that an impaired reverse cholesterol transport (RCT) from peripheral cells to the liver, which is mediated by HDL, might influence the susceptibility to infectious disease.
The goal is to measure the cholesterol efflux capacity of HDL – the key initial step of RCT – in a large cohort of patients with moderate chronic kidney disease (CKD). Patients with CKD are an interesting patient collective for studying susceptibility to infectious disease since they have a high risk for inflammation and infections which are often life-limiting. A major task will be the adaption, establishment and validation of a recently published RCT assay to a medium-to-high throughput setup. A further task will be to conduct a genome-wide association study to search for genetic variants associated with the findings. Depending on the results of these experiments, further parameters which influence RCT (e.g. levels of apolipoprotein A-IV and metabolomics data) might also be investigated.
