1. APOC3 LOF heterozygotes have lower IVD and IHD risks due to lower RC
Overall 41% lower IVD risk – 37% mediated by lower RC
P value for the indirect effect, P=6×10−37
Overall 36% lower IHD risk – 54% mediated by lower RC
P value for the indirect effect, P=1×10−37
In the Copenhagen Studies, APOC3 LOF heterozygotes versus non-carriers had a 41% RR of IVD (HR: 0.59; 95% CI, 0.41–0.86; P=0.007) and a corresponding 36% reduction in risk of IHD (HR: 0.64; 95% CI, 0.41–0.99; P=0.04). The lower levels of remnant cholesterol in APOC3 LOF heterozygotes versus non-carriers mediated 37% of the lower IVD risk (P value for the indirect effect, P=6×10−37) and 54% of the lower IHD risk (P value for the indirect effect, P=1×10−37), whereas the 4% lower levels of LDL-c mediated only 1% and 2% of the lower risks.
LOF: loss-of-function; IVD: ischemic vascular disease; IHD: ischemic heart disease; RC: remnant cholesterol; LDL-c: low density lipoprotein cholesterol;
Wulff AB, et al. Arterioscler Thromb Vasc Biol 2018