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Isolation of Mouse Interstitial Valve Cells to Study the Calcification of the Aortic Valve In Vitro
Published on: May 10, 2021
Genetic associations with valvular calcification and aortic stenosis
George Thanassoulis1, Catherine Y Campbell, David S Owens
1Department of Medicine and the Research Institute, McGill University Health Centre, Montreal.
The New England Journal of Medicine
|February 8, 2013
Summary
Genetic variations in the LPA gene are linked to aortic-valve calcification and aortic stenosis. This highlights the role of lipoprotein(a) in heart valve disease development.
Area of Science:
- Genomics and Cardiovascular Disease
- Genetic Epidemiology
- Biomarkers of Atherosclerosis
Background:
- Valvular calcification is a critical precursor to clinical valve disease, yet its genetic underpinnings remain largely unexplored.
- Understanding genetic factors can elucidate disease mechanisms and identify novel therapeutic targets for valvular heart disease.
Purpose of the Study:
- To identify genetic variants associated with valvular calcification using genomewide association studies (GWAS).
- To investigate the causal role of lipoprotein(a) [Lp(a)] in aortic-valve calcification and subsequent clinical aortic stenosis.
Main Methods:
- Conducted GWAS for aortic-valve calcification and mitral annular calcification in European ancestry cohorts (n=6942 and n=3795, respectively).
- Replicated significant findings in independent cohorts across diverse ethnic groups (White European, African-American, Hispanic-American).
- Assessed the association of LPA genotype with Lp(a) levels and prospective outcomes including incident aortic stenosis and aortic-valve replacement.
Main Results:
- A single nucleotide polymorphism (SNP) rs10455872 in the LPA locus reached genomewide significance for aortic-valve calcification (OR=2.05, P=9.0×10(-10)), replicated across ethnic groups.
- Genetically predicted Lp(a) levels were associated with aortic-valve calcification, supporting a causal role for Lp(a).
- LPA genotype was significantly associated with incident aortic stenosis and aortic-valve replacement in Swedish and Danish cohorts.
- Two SNPs near IL1F9 showed genomewide significance for mitral annular calcification but lacked consistent replication.
Conclusions:
- Genetic variation in the LPA locus, acting through Lp(a) levels, is a significant risk factor for aortic-valve calcification across diverse populations.
- This genetic association extends to the development of clinical aortic stenosis, underscoring Lp(a) as a key mediator in valvular heart disease.
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