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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.

Coronary Artery Disease–Associated LIPA Coding Variant rs1051338 Reduces Lysosomal Acid Lipase Levels and Activity in Lysosomes