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Peer-reviewedCC BY 4.0PLOS One

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

  • Citrawati Dyah Kencono Wungu1
  • Hendri Susilo2
  • Jesselyn Wijaya3
  • Cleodylon R. Susanto4
  • Kevin Kevin5
  • David Nugraha6
  • Delvac Oceandy7
7 affiliations
  1. 1Department of Physiology and Medical Biochemistry, Faculty of Medicine, Universitas Airlangga, Surabaya, Indonesia
  2. 2Institute of Tropical Disease, Universitas Airlangga, Surabaya, Indonesia
  3. 3Department of Cardiology and Vascular Medicine, Faculty of Medicine, Universitas Airlangga, Surabaya, Indonesia
  4. 4Cardiovascular and Cardiometabolic Science Research Group, Faculty of Medicine, Universitas Airlangga, Surabaya, Indonesia
  5. 5Department of Cardiology and Vascular Medicine, Universitas Airlangga Hospital, Surabaya, Indonesia
  6. 6Medical Program, Faculty of Medicine, Universitas Airlangga, Surabaya, Indonesia
  7. 7Division of Cardiovascular Sciences, Faculty of Biology Medicine and Health, University of Manchester, Manchester, United Kingdom
Open at sourceDOICite

Abstract

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.

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Cite

BibTeXRIS
BibTeX
@article{wungu2026bag3,
  title = {{BAG3 genetic variant is associated with heart failure with preserved ejection fraction phenotypes}},
  author = {Citrawati Dyah Kencono Wungu and Hendri Susilo and Jesselyn Wijaya and Cleodylon R. Susanto and Kevin Kevin and David Nugraha and Delvac Oceandy},
  journal = {PLOS One},
  year = {2026},
  month = nov,
  doi = {10.1371/journal.pone.0361206},
  url = {https://doi.org/10.1371/journal.pone.0361206},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - BAG3 genetic variant is associated with heart failure with preserved ejection fraction phenotypes
AU  - Citrawati Dyah Kencono Wungu
AU  - Hendri Susilo
AU  - Jesselyn Wijaya
AU  - Cleodylon R. Susanto
AU  - Kevin Kevin
AU  - David Nugraha
AU  - Delvac Oceandy
PY  - 2026
DA  - 2026/11/03
JO  - PLOS One
DO  - 10.1371/journal.pone.0361206
UR  - https://doi.org/10.1371/journal.pone.0361206
AB  - 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.
SN  - 1932-6203
ER  -