Study finds shared genetic risk factors link IgAN, heart conditions
Researchers ID existing medications that could treat co-occurring conditions
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IgAN shares genetic links with some heart and metabolic conditions. (Image from iStock)
Immunoglobulin A nephropathy (IgAN) shares genetic risk factors with many cardiovascular and metabolic conditions, a study found.
The findings may help explain why people with IgAN are at high risk of health complications such as heart disease, researchers said. Based on these shared genetic profiles, they identified several existing medications that might simultaneously address IgAN and co-occurring conditions.
“Our findings not only advance the current understanding of the genetic mechanisms underlying IgAN and its metabolic comorbidities but also lay a critical foundation for the development of more precise risk assessment tools and innovative therapeutic strategies targeting shared [disease-driving] pathways,” the scientists wrote.
The study, “Shared genetics of IgA nephropathy and cardiometabolic diseases revealed by integrative genomic analysis,” was published in Renal Failure.
IgAN is marked by progressive kidney damage and is a leading cause of kidney failure. Increasing evidence suggests that the disorder also affects other parts of the body, and people with IgAN are at a significantly increased risk of cardiometabolic diseases relative to the general population.
Exploring shared links
Cardiometabolic conditions are a group of interconnected disorders, combining metabolic diseases like obesity and diabetes with cardiovascular issues such as high blood pressure and heart disease. IgAN patients are more likely to develop high blood pressure, abnormal levels of lipids (fatty molecules), obesity, metabolic disturbances, and cardiovascular issues.
It’s not clear why IgAN is associated with cardiometabolic diseases, and the causes of IgAN are not well understood. However, available data suggest that genetics play a key role in IgAN risk. Genetics have also been shown to influence the development of many cardiometabolic diseases.
Scientists in China wanted to explore whether shared genetic risk factors might explain the association between IgAN and cardiometabolic diseases. To do this, they analyzed data from large genetic risk factor databases.
The researchers looked for overlap in genetic risk factors for IgAN and 21 cardiometabolic diseases, 13 metabolic traits (such as blood lipid levels), and 11 immune cell features.
They found significant genetic associations between IgAN and 21 clinical traits, including 10 cardiometabolic conditions. Cardiovascular diseases showed the strongest genetic association with IgAN. Metabolic conditions, such as diabetes and obesity, also shared genetic risk factors with IgAN.
When looking at specific genetic variants shared among diseases, the team found that IgAN and coronary artery disease (which is marked by the buildup of fatty molecules in the arteries that supply the heart) exhibited the greatest number of shared variants (nine).
But “the genetic overlap between IgAN and physiological traits was more pronounced,” the researchers wrote, adding that 29 IgAN-related genetic variants were also associated with blood levels of triglycerides (a type of lipid).
Further analyses showed that many of the shared genetic variants were linked to pathways involved in lipid metabolism and blood pressure regulation.
“We identified a shared genetic architecture between IgAN and key risk factors such as blood pressure and lipid profiles,” the researchers wrote. “These findings provide robust evidence supporting the central role of lipid metabolism dysregulation in the development and progression of [blood vessel-related] complications associated with IgAN.”
The researchers conducted computer-based tests to screen for drugs that may modulate pathways associated with both IgAN and co-occurring cardiometabolic diseases in patients.
These tests identified dozens of potential candidates, including immunosuppressive medications such as prednisone (a corticosteroid), lipid-lowering agents such as statins, and blood-clotting preventives such as aspirin.
This “suggests that lipid-lowering agents – including statins – may hold promise as potential therapeutic interventions for IgAN-related [cardiometabolic] conditions,” the researchers wrote. “This highlights a novel and clinically relevant direction for future research focusing on lipid metabolic disorders in patients with IgAN.”
The scientists noted that the analyses were entirely computer-based, and they emphasized a need for additional experiments to validate the findings.
