Fatty Liver and CAD Share Genetic Drivers

Scientists have long known that nonalcoholic fatty liver disease (NAFLD) and coronary artery disease (CAD) often appear together, but the exact biological reasons why have remained unclear. This study aimed to uncover shared genetic and molecular mechanisms, especially related to how the body processes fats (lipids).

In a recent study published in IUBMB Life, a team of researchers analyzed several large datasets containing genetic information from patients with NAFLD and CAD. Using advanced bioinformatics tools, they searched for genes involved in both diseases and examined how these genes interacted with lipid metabolism, immune cells, and biological pathways.

They also studied individual cells using single-cell sequencing to see how these genes behaved in specific types of cells within the liver and blood vessels.

The researchers identified three key genes that appear to play a significant role in both fatty liver disease and heart disease: GPD, MVK, and PIK3R2. These genes were highly active in immune cells related to fat and bile acid metabolism in NAFLD, active in oxidative stress pathways in CAD, and strongly correlated with other known genes involved in liver and heart health.

They also found that:

• GPD1 had a strong connection to PNPLA3, a gene already linked to liver disease.
• PIK3R2 showed a negative link to MIR21 and LPA, which are involved in heart disease processes.
• PIK3R2 interacts with 38 known drugs, and MVK interacts with at least one, pointing to potential drug targets.

These findings deepen our understanding of why fatty liver disease and heart disease often go hand-in-hand. The study suggests that targeting these three genes—especially PIK3R2—could open the door to new treatments that address both diseases at once. It also reinforces the idea that immune system activity and fat metabolism are tightly linked in chronic diseases.