Research highlight: Using metabolomics and genetics to compare CETP Inhibitors with Statins

Research Highlight: Ference et al. Association of Genetic Variants Related to CETP Inhibitors and Statins With Lipoprotein Levels and Cardiovascular Risk. JAMA 2017;318(10):947-956 doi: 10.1001/jama.2017.11467

In previous studies, cholesteryl ester transfer protein (CETP) inhibitors have been highlighted for therapeutic use in treating cardiovascular disease (CVD). Recent evidence has shed doubt on the clinical effectiveness of some CETP inhibitors that show lower low-density lipoprotein cholesterol (LDL-C) levels without reducing cardiovascular events. 

In this paper, researchers used random segregation of genetic variants in CETP and HMGCR genes (Mendelian Randomization) to study their causal effects of on metabolic markers apolipoprotein B (apoB) and LDL-C. Genetic variants in genes that encode the targets of CETP inhibitors (CETP) and statins (HMGCR) were associated with different reductions in LDL-C and apoB levels – with the corresponding risk of cardiovascular events being proportional to reduction in apoB levels, but less than expected for LDL-C changes. 

These results indicate that the clinical benefit of reducing LDL-C levels may depend on a corresponding reduction in the amount of apoB-containing lipoprotein particles, and that CETP inhibitors may be more effective without concurrent statin therapy. 

This study is an example of Nightingale's NMR metabolomics platform being applied in CVD research. Nightingale's platform has been successfully applied to a wide range of research applications and has been featured in over 100 peer-reviewed studies, in leading biomedical journals. In this paper, metabolic profiling was utilized to investigate drug target mechanism of action, using genetic variants as a proxy for therapy. Nightingale’s platform was used to measure levels of LDL-C and apoB.

Extra reading:

You can find our take on the findings of this paper here, along with a JAMA editorial feature here.