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

Judita Knez, Erika Salvi, Valerie Tikhonoff, Katarzyna Stolarz-Skrzypek, Andrew Ryabikov, Lutgarde Thijs, Daniele Braga, Malgorzata Kloch-Badelek, Sofia Malyutina, Edoardo Casiglia, Danuta Czarnecka, Kalina Kawecka-Jaszcz, Daniele Cusi, Tim Nawrot, Jan A. Staessen, Tatiana Kuznetsova*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review


Background: Left ventricular (LV) function depends on the activity of transmembrane electrolyte transporters. Failing human myocardium has lower Na+/K+ ATPase expression and higher intracellular sodium concentrations. The ATP12A gene encodes a catalytic subunit of an ATPase that can function as a Na+/K+ pump. We, therefore, investigated the association between LV function and common genetic variants in ATP12A. Methods: A random sample of 1166 participants (53.7% women; mean age 49.5 years, 44.8% hypertensive) was recruited in Belgium, Poland, Italy and Russia. We measured transmitral early and late diastolic velocities (E and A) by pulsed wave Doppler, and mitral annular velocities (e' and a') by tissue Doppler. Using principal component analysis, we summarized 7 Doppler indexes - namely, E, A, e' and a' velocities, and their ratios (E/A, e'/a', and E/e') - into a single diastolic score. We genotyped 5 tag SNPs (rs963984, rs9553395, rs10507337, rs12872010, rs2071490) in ATP12A. In our analysis we focused on rs10507337 because it is located within a transcription factor binding site. Results: In the population-based analyses while adjusting for covariables and accounting for family clusters and country, rs10507337 C allele carriers had significantly higher E/A (P = 0.003), e' (P = 5.8x10(-5)), e'/a' (P = 0.003) and diastolic score (P = 0.0001) compared to TT homozygotes. Our findings were confirmed in the haplotype analysis and in the family-based analyses in 74 informative offspring. Conclusions: LV diastolic function as assessed by conventional and tissue Doppler indexes including a composite diastolic score was associated with genetic variation in ATP12A. Further experimental studies are necessary to clarify the role of ATP12A in myocardial relaxation.
Original languageEnglish
Article number121
JournalBMC Medical Genetics
Publication statusPublished - 4 Nov 2014


  • Epidemiology
  • Echocardiography
  • Diastolic function
  • ATP12A

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