In order to investigate the impact of increasing HDL-C levels through use of CETP inhibitors on detailed metabolic profiles, Millwood and colleagues used genetic variants in the CETP gene to assess the effects of lowered CETP activity on CVD risk, along with other factors that could indicate potential on-target effects (e.g. risk of eye diseases).
Five CETP variants, including an East Asian specific loss-of-function variant (rs2303790), were selected for investigation from the China Kadoorie Biobank (CKB) cohort of 151,217 Chinese participants. Among these individuals, 4657 participants provided blood samples which were analyzed using high-throughput NMR-based metabolomics to provide metabolic profiling data. CETP variants were found to be strongly associated with higher concentrations of HDL-C but did not lower LDL-C levels in this population.