Association of Genetically Enhanced Lipoprotein Lipase-Mediated Lipolysis and Low-Density Lipoprotein Cholesterol-Lowering Alleles With Risk of Coronary Disease and Type 2 Diabetes
Publication: JAMA Cardiology
Lotta LA, Stewart ID, Sharp SJ, Day FR, Burgess S, Luan J, et al.
19 September 2018
Are genetically determined differences in lipoprotein lipase (LPL)–mediated lipolysis and low-density lipoprotein cholesterol (LDL-C)–lowering pathways independently associated with risk of coronary disease and diabetes?
In this genetic association study including 392 220 people, triglyceride-lowering alleles in LPL or its inhibitor ANGPTL4 were associated with lower risk of coronary artery disease and type 2 diabetes in a consistent fashion across quantiles of the population distribution of LDL-C–lowering alleles.
For a given genetic difference in LDL-C, the association with lower risk of coronary disease conveyed by rare loss-of-function variants in ANGPTL3, which are associated with lower LDL-C levels and enhanced LPL lipolysis, was greater than that conveyed by other LDL-C–lowering genetic mechanisms.
Meaning LPL-mediated lipolysis and LDL-C–lowering mechanisms independently contribute to the risk of coronary disease and diabetes, which supports the development of LPL-enhancing agents for use in the context of LDL-C–lowering therapy.
