Genetic predisposition to calcific aortic stenosis and mitral annular calcification

Area of Science:

• Cardiovascular Genetics
• Molecular Cardiology
• Genetics of Valvular Heart Disease

Background:

• Valvular calcification is an early indicator of valvular heart disease and often runs in families.
• The genetic underpinnings of valvular calcification, particularly predictive markers, remain largely unexplored.
• Understanding genetic predispositions is crucial for early identification and management of valvular heart disease.

Purpose of the Study:

• To review and assess the impact of gene polymorphisms on the risk and severity of aortic stenosis and mitral annular calcification.
• To categorize genetic markers based on their evidential association with valvular stenosis.
• To identify key genetic polymorphisms associated with valvular calcific stenosis.

Main Methods:

• Systematic review of existing investigations on gene polymorphisms and valvular calcification.
• Categorization of gene polymorphisms into groups based on the level of evidence linking them to valvular stenosis.
• Analysis of specific polymorphisms within genes such as apoB, ACE, IL10, LPA, ORα, CaSR, PON1, MYO7A, AGTR1, ELN, IL1F9, VDR, apoE, and PTH.

Main Results:

• Gene polymorphisms were classified into three evidence-based groups regarding their association with valvular stenosis.
• High evidence of association was found for apoB (XbaI, rs1042031, rs6725189), ACE (rs4340), IL10 (rs1800896, rs1800872), and LPA (rs10455872).
• Moderate and low levels of evidence linked other polymorphisms (e.g., ORα, CaSR, IL10, PON1, VDR, apoE) to valvular calcification risk and aortic stenosis.

Conclusions:

• Specific gene polymorphisms, notably apoB, ACE, IL10, and LPA, are strongly associated with valvular calcific stenosis.
• Several other gene polymorphisms demonstrate moderate to low evidence of association with the risk of calcific valve stenosis and aortic stenosis.
• These findings highlight the potential of genomic markers for predicting valvular calcification and guiding early interventions in valvular heart disease.