Coronary Artery Disease-Associated <i>LIPA</i> Coding Variant rs1051338 Reduces Lysosomal Acid Lipase Levels and Activity in Lysosomes.

ABSTRACT:

Objective

Genome-wide association studies have linked variants at chromosome 10q23 with increased coronary artery disease risk. The disease-associated variants fall in LIPA, which encodes lysosomal acid lipase (LAL), the enzyme responsible for lysosomal cholesteryl ester hydrolysis. Loss-of-function mutations in LIPA result in accelerated atherosclerosis. Surprisingly, the coronary artery disease variants are associated with increased LIPA expression in some cell types. In this study, we address this apparent contradiction.

Approach and results

We investigated a coding variant rs1051338, which is in high linkage disequilibrium (r²=0.89) with the genome-wide association study lead-associated variant rs2246833 and causes a nonsynonymous t

SUBMITTER: Morris GE 

PROVIDER: S-EPMC5444428 | biostudies-literature | 2017 Jun

REPOSITORIES: biostudies-literature