BAG3 Mutations Linked with Adverse Cardiovascular Outcomes

Mutations in unique Bcl2-associated anthanogene 3 (BAG3) functional genetic variants in individuals of African ancestry were associated with an increased risk for adverse cardiovascular outcomes, new study results suggest. 

Researchers for the multicohort study published online in JAMA Cardiology used DNA from African American individuals with dilated cardiomyopathy from three different clinical trials (the GRAHF, IMAC-2 and GRACE studies). The primary study endpoint included the prevalence of BAG3 mutations in African American individuals and event-free survival in those with functional BAG3 mutations.  

According to the results, four BAG3 mutations were identified and were expressed in populations of African descent, but not a reference population of individuals of European ancestry (P<0.001). Additionally, the presence of BAG3 variants was associated with a two-fold increase in the risk for adverse cardiovascular events (HR=1.97; 95% CI, 1.19 to 3.24]; P=0.01). 

“This study demonstrates that genetic variants in BAG3 found almost exclusively in individuals of African ancestry were not causative of disease but were associated with a negative outcome in patients with a dilated cardiomyopathy through modulation of the function of BAG3,” the researchers wrote. “The results emphasize the importance of biological differences in causing phenotypic variance across diverse patient populations, the need to include diverse populations in genetic cohorts, and the importance of determining the pathogenicity of genetic variants.” 

Source: JAMA Cardiology