Heart failure & cardiomyopathies
Myocardial Fibrosis and Cardiomyopathy Risk: A Genetic Link in the MESA
Authors' conclusion
Common genetic variation in SMARCB1 previously associated with risk for cardiomyopathies and increased LV wall thickness is associated with increased cardiac magnetic resonance imaging-based myocardial fibrosis and increased TGF-β1 mediated myocardial fibrosis in vitro.
Study context
- Population
- MESA participants with T1-mapping CMR (extracellular volume) and genotyping
- Participants
- 1,255 participants
- Outcome
- Log extracellular volume (%) regressed on 50 candidate SNPs for HCM, DCM and LV traits
Methodological detailscandidate SNP analysis, fixed-effect meta-analysis of ancestry-specific results, gene knockdown in human cardiac fibroblasts
- Candidate SNP analysis
- Fixed-effect meta-analysis of ancestry-specific results
- Gene knockdown in human cardiac fibroblasts
Main finding
As reported in the abstract
Extracellular volume (myocardial fibrosis)
- SMARCB1 rs2186370 (DCM/HCM risk variant) associated with increased extracellular volume, adjusted
- P=0.0002
- SMARCB1 rs2070458 (left ventricular (LV) wall thickness and mass locus) associated with increased extracellular volume
- P=0.0002
Further findings
SMARCB1 expression in human LV tissue
- Variants are strong expression quantitative loci; genotype-dependent decreased SMARCB1 expression
- P = 7.3×10-22
SMARCB1 knockdown in human cardiac fibroblasts
- Increased TGF-β1-mediated α-smooth muscle actin and collagen expression
Original publication
Myocardial Fibrosis and Cardiomyopathy Risk: A Genetic Link in the MESA. Circ Heart Fail. Published 1 August 2023. doi:10.
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