Underlining the Molecular Mechanism of Nonalcoholic Fatty Liver Disease and Coronary Artery Disease in Lipid Metabolism by Combining Multiple Sets of Data Sets

Nonalcoholic fatty liver disease (NAFLD) is closely associated with coronary artery disease (CAD); however, their shared genetic traits and molecular mechanisms in lipid metabolism remain unclear. In this study, we identified that the differentially expressed genes in NAFLD and CAD intersected with lipid metabolism genes to obtain three key genes—GPD1, MVK, and PIK3R2. Data from the GeneCards database indicated a significant correlation between NAFLD-related regulatory genes and the expression levels of these key genes. Notably, GPD1 showed a significant positive correlation with PNPLA3 (r = 0.715), while PIK3R2 exhibited a significant negative correlation with MIR21 (r = −0.691). Similarly, CAD regulatory genes were significantly correlated with the expression levels of these key genes; GPD1 showed a significant positive correlation with APOA1 (r = 0.751), and PIK3R2 had a significant negative correlation with LPA (r = −0.362). Additionally, single-cell sequencing analysis of NAFLD showed that GPD1, MVK, and PIK3R2 had higher activity in cells with a high expression of bile acid metabolism genes in the immune pathway. In CAD, GPD1 showed higher activity in cells with high oxidative phosphorylation in the immune pathway. Finally, we found that one drug interacted with MVK, while 38 drugs interacted with PIK3R2. This study highlights GPD1, MVK, and PIK3R2 as key genes involved in NAFLD, CAD, and lipid metabolism, suggesting potential targets for further mechanistic studies and novel therapeutic approaches for patients with NAFLD and CAD.