Altered expression of lysosomal hydrolase, acid α-glucosidase, gene in coronary artery disease.

Abstract

Coronary artery disease (CAD) is a common complex disease caused by atherosclerosis. Autophagy is a cellular degradation process that delivers long-lived macromolecules and dysfunctional organelles into lysosomes for digestion. Autophagy regulates lipid and cholesterol metabolism. We have previously shown that expression of autophagic and lysosomal genes is altered in CAD patients. In this study, we investigated gene expression of a lysosomal hydrolase, acid α-glucosidase (GAA), in CAD patients and controls. GAA gene expression was examined in large cohorts of CAD patients (n=248) and ethnically matched controls (n=208). GAA enzymatic activity, protein levels, and transcript levels were determined and compared between CAD patients and controls. GAA activities in CAD patients were significantly elevated (P<0.05) compared with controls. Consistently, GAA transcription levels were also significantly increased in CAD patients (P<0.01). Multivariate logistic regression analyses (GAA transcript level, hypertension, diabetes, and smoking) revealed that GAA transcript levels were strongly associated with CAD (odds ratio 5.93, 95% confidence interval 2.98-11.78, P=3.89×10(-7)). GAA protein levels were insignificantly increased in CAD patients (P>0.05), likely due to assay insensitivity. Compared with controls, GAA gene expression levels in CAD patients were significantly increased, suggesting that GAA may be involved in the CAD development.