BAG3 genetic variant is associated with heart failure with preserved ejection fraction phenotypes

Genetic variations are involved in determining heart failure (HF) phenotypes. While variants within the BAG3 gene have been associated with HF in European populations, the impact of specific single nucleotide polymorphisms (SNPs) within the BAG3 gene in determining phenotypes of HF with preserved ejection fraction (HFpEF) in Southeast Asian populations is unknown. Therefore, in this study, we identified BAG3 SNPs and investigated their biological and clinical relevance in determining HFpEF phenotypes among an Indonesian HFpEF cohort. We conducted a study involving 36 patients with HFpEF and 30 healthy individuals. We detected the presence of rs196326 and rs2240777 SNPs in our cohort. However, the rs2234962 polymorphism, which has been associated with HF and cardiomyopathy in Western populations, was absent in our Indonesian cohort. We found that the rs196326 SNP was significantly associated with relative wall thickness (RWT), with patients carrying the CG genotype displayed significantly lower RWT. Additionally, the rs196326 CG/GG genotypes were correlated with higher serum N-terminal pro B-type natriuretic peptide (NT-proBNP) and lower Caspase-3 levels. Our study showed that the BAG3 rs196326 polymorphism was significantly associated with HFpEF phenotypes in the Indonesian population. This highlights the importance of identifying population-specific as genetic markers of disease severity.