Title: Left ventricular diastolic function associated with common genetic variation in ATP12A in a general population
Authors: Knez, Judita
Salvi, Erika
Tikhonoff, Valérie
Stolarz-Skrzypek, Katarzyna
Ryabikov, Andrew
Thijs, Lutgarde
Braga, Daniele
Kloch-Badelek, Malgorzata
Malyutina, Sofia
Casiglia, Edoardo
Czarnecka, Danuta
Kawecka-Jaszcz, Kalina
Cusi, Daniele
Nawrot, Tim
Staessen, Jan A
Kuznetsova, Tatiana # ×
Issue Date: Nov-2014
Publisher: BioMed Central
Series Title: BMC Medical Genetics vol:15 issue:1 pages:121
Article number: 121
Abstract: BackgroundLeft 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.MethodsA 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.ResultsIn 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.ConclusionsLV 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.
ISSN: 1471-2350
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Hypertension and Cardiovascular Epidemiology
Environment and Health - miscellaneous
Department of Cardiovascular Sciences - miscellaneous
× corresponding author
# (joint) last author

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