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Title: Left ventricular diastolic function associated with common genetic variation in ATP12A in a general population
Authors: Knez, Judita
Salvi, Erika
Tikhonoff, Valerie
Stolarz-Skrzypek, Katarzyna
Ryabikov, Andrew
Thijs, Lutgarde
Braga, Daniele
Kloch-Badelek, Malgorzata
Malyutina, Sofia
Casiglia, Edoardo
Czarnecka, Danuta
Kawecka-Jaszcz, Kalina
Cusi, Daniele
Staessen, Jan A.
Kuznetsova, Tatiana
Issue Date: 2014
Abstract: 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.
Notes: [Knez, Judita; Thijs, Lutgarde; Staessen, Jan A.; Kuznetsova, Tatiana] Univ Leuven, Res Unit Hypertens & Cardiovasc Epidemiol, KU Leuven Dept Cardiovasc Sci, Leuven, Belgium. [Knez, Judita] Univ Clin Ctr Ljubljana, Dept Internal Med, Div Hypertens, Ljubljana, Slovenia. [Salvi, Erika; Braga, Daniele; Cusi, Daniele] Univ Milan, Dept Hlth, Milan, Italy. [Salvi, Erika; Braga, Daniele; Cusi, Daniele] Fdn Filarete, Genom & Bioinformat Platform, Milan, Italy. [Tikhonoff, Valerie; Casiglia, Edoardo] Univ Padua, Dept Med, Padua, Italy. [Tikhonoff, Valerie] UCL, MRC Unit Lifelong Hlth & Ageing, London, England. [Stolarz-Skrzypek, Katarzyna; Kloch-Badelek, Malgorzata; Czarnecka, Danuta; Kawecka-Jaszcz, Kalina] Jagiellonian Univ, Coll Med, Dept Cardiol Intervent Elect & Hypertens 1, Krakow, Poland. [Ryabikov, Andrew; Malyutina, Sofia] Inst Internal & Prevent Med, Novosibirsk, Russia. [Ryabikov, Andrew; Malyutina, Sofia] Novosibirsk State Med Univ, Novosibirsk, Russia. [Nawrot, Tim] Katholieke Univ Leuven, Dept Publ Hlth Occupat & Environm Med, Leuven, Belgium. [Nawrot, Tim] Hasselt Univ, Ctr Environm Sci, Diepenbeek, Belgium. [Staessen, Jan A.] Maastricht Univ, Dept Epidemiol, Maastricht, Netherlands.
Keywords: Epidemiology; Echocardiography; Diastolic function; ATP12A;epidemiology; echocardiography; diastolic function; ATP12A
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e-ISSN: 1471-2350
DOI: 10.1186/s12881-014-0121-6
ISI #: 000345714600001
Rights: © 2014 Knez et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver ( applies to the data made available in this article, unless otherwise stated.
Category: A1
Type: Journal Contribution
Validations: ecoom 2015
Appears in Collections:Research publications

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