Left ventricular diastolic function associated with common genetic variation in ATP12A in a general population

Area of Science:

• Cardiovascular Genetics
• Molecular Cardiology
• Physiology

Background:

• Left ventricular (LV) function is influenced by transmembrane electrolyte transporters.
• Reduced Na(+)/K(+) ATPase expression and elevated intracellular sodium characterize failing human myocardium.
• The ATP12A gene encodes a catalytic subunit of a Na(+)/K(+) pump, suggesting its potential role in cardiac function.

Purpose of the Study:

• To investigate the association between left ventricular (LV) diastolic function and common genetic variants in the ATP12A gene.
• To explore the relationship between specific ATP12A single nucleotide polymorphisms (SNPs) and Doppler-derived measures of diastolic function.
• To determine if genetic variations in ATP12A influence myocardial relaxation.

Main Methods:

• Recruited 1166 participants from a multi-center European population.
• Assessed LV diastolic function using transmitral (E, A) and mitral annular (e', a') velocities via Doppler echocardiography.
• Genotyped 5 tag SNPs in ATP12A, focusing on rs10507337 due to its location within a transcription factor binding site, and calculated a composite diastolic score.

Main Results:

• Carriers of the rs10507337 C allele exhibited significantly higher E/A, e', e'/a', and composite diastolic scores compared to TT homozygotes (P < 0.004).
• These findings were robust, confirmed by haplotype and family-based analyses.
• The C allele of rs10507337 is associated with enhanced left ventricular diastolic function.

Conclusions:

• Genetic variation within the ATP12A gene is associated with left ventricular diastolic function.
• Doppler-derived indices, including a composite diastolic score, reflect this genetic association.
• Further research is warranted to elucidate the precise mechanisms by which ATP12A influences myocardial relaxation.