Dataset Information

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

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 = 5.8×10(-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.

SUBMITTER: Knez J

PROVIDER: S-EPMC4411923 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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

Knez Judita J Salvi Erika E Tikhonoff Valérie V Stolarz-Skrzypek Katarzyna K Ryabikov Andrew A Thijs Lutgarde L Braga Daniele D Kloch-Badelek Malgorzata M Malyutina Sofia S Casiglia Edoardo E Czarnecka Danuta D Kawecka-Jaszcz Kalina K Cusi Daniele D Nawrot Tim T Staessen Jan A JA Kuznetsova Tatiana T

BMC medical genetics 20141104

<h4>Background</h4>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.<h4>Methods</h4>A random sample of 1166 participants (53.7% women; mean ...[more]

PMID: 25366262

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Project description:BackgroundAir pollution is a growing public health concern of global significance. Till date, few studies have explored the associations between air pollutants and cardiac imaging phenotypes. In this study, we aim to explore the association of ambient air pollution and abnormal left ventricular diastolic function (ALVDF) among a large-scale free-living population.MethodsThe participants were from a national representative large-scale cross-sectional study, i.e., the China Hypertension Survey (CHS), 2012-15. After exclusion, 25,983 participants from 14 provinces and 30 districts in China were included for the final analysis. The annual average ambient PM2.5, PM10 and NO2 concentrations were obtained from the chemical data assimilation system (ChemDAS). The clinical evaluation of left ventricular function was conducted in the survey field which was based on echocardiography. Grading diastolic dysfunction was based on Recommendations for the evaluation of left ventricular diastolic function by echocardiography (2009).ResultsThe mean age of 25,983 participants was 56.8 years, 46.5% were male, and the crude prevalence of GradeI-III ALVDF were 48.1%, 1.6% and 1.1%, respectively. The ORs (95% CI) for ALVDF in the fully adjusted model were 1.31 (1.11-1.56), 1.11 (1.01-1.21) and 1.18 (0.90-1.54) for an increase of 10 μg/m3 of PM2.5, PM10 and NO2, respectively. And for different grades of ALVDF, elevated concentration of PM2.5 and PM10 exposures significantly increased the risk of gradeIinstead of gradeII ~ III ALVDF. There was a positive linear and "J" shape concentration-response association between annual average ambient PM2.5 and NO2 and the ALVDF risk assessed by the restricted cubic spline. The exposure level of most participants to PM10 was less than 130 μg/m3, and the risk of ALVDF increased significantly with the concentration rise.ConclusionsThis large-scale nationwide population study demonstrated a significantly positive association between ambient PM2.5, PM10 and NO2 with ALVDF, especially for mild ALVDF. The functional abnormality may partially explain the enhanced cardiovascular morbidity and mortality associated with air pollution, which highlights the importance of appropriate interventions to reduce ambient air pollution in China.

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

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

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