Functional Characterization of LIPA (Lysosomal Acid Lipase) Variants Associated With Coronary Artery Disease.

ABSTRACT:

Objective

LIPA (lysosomal acid lipase) mediates cholesteryl ester hydrolysis, and patients with rare loss-of-function mutations develop hypercholesterolemia and severe disease. Genome-wide association studies of coronary artery disease have identified several tightly linked, common intronic risk variants in LIPA which unexpectedly associate with increased mRNA expression. However, an exonic variant (rs1051338 resulting in T16P) in linkage with intronic variants lies in the signal peptide region and putatively disrupts trafficking. We sought to functionally investigate the net impact of this locus on LIPA and whether rs1051338 could disrupt LIPA processing and function to explain coronary artery disease risk. Approach and Results: In monocytes isolated from a large cohort of

SUBMITTER: Evans TD 

PROVIDER: S-EPMC7050600 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature