Endothelial nitric oxide synthase single nucleotide polymorphism and left ventricular function in early chronic kidney disease

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Endothelial nitric oxide synthase single nucleotide polymorphism and left ventricular function in early chronic kidney disease. / Chand, Sourabh; Chue, Colin D.; Edwards, Nicola C.; Hodson, James; Simmonds, Matthew J.; Hamilton, Alexander; Gough, Stephen C. L.; Harper, Lorraine; Steeds, Rick P.; Townend, Jonathan N.; Ferro, Charles J.; Borrows, Richard.

In: PLoS ONE, Vol. 10, No. 1, e0116160, 22.01.2015.

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@article{fc8f3ee6a9764ee3aaa92769c7e2e555,
title = "Endothelial nitric oxide synthase single nucleotide polymorphism and left ventricular function in early chronic kidney disease",
abstract = "BackgroundChronic kidney disease (CKD) is associated with accelerated cardiovascular disease and heart failure. Endothelial nitric oxide synthase (eNOS) Glu298Asp single nucleotide polymorphism (SNP) genotype has been associated with a worse phenotype amongst patients with established heart failure and in patients with progression of their renal disease. The association of a cardiac functional difference in non-dialysis CKD patients with no known previous heart failure, and eNOS gene variant is investigated.Methods140 non-dialysis CKD patients, who had cardiac magnetic resonance (CMR) imaging and tissue doppler echocardiography as part of two clinical trials, were genotyped for eNOS Glu298Asp SNP retrospectively.ResultsThe median estimated glomerular filtration rate (eGFR) was 50mls/min and left ventricular ejection fraction (LVEF) was 74% with no overt diastolic dysfunction in this cohort. There were significant differences in LVEF across eNOS genotypes with GG genotype being associated with a worse LVEF compared to other genotypes (LVEF: GG 71%, TG 76%, TT 73%, p = 0.006). After multivariate analysis, (adjusting for age, eGFR, baseline mean arterial pressure, contemporary CMR heart rate, total cholesterol, high sensitive C-reactive protein, body mass index and gender) GG genotype was associated with a worse LVEF, and increased LV end-diastolic and systolic index (p = 0.004, 0.049 and 0.009 respectively).ConclusionseNOS Glu298Asp rs1799983 polymorphism in CKD patients is associated with relevant sub-clinical cardiac remodelling as detected by CMR. This gene variant may therefore represent an important genetic biomarker, and possibly highlight pathways for intervention, in these patients who are at particular risk of worsening cardiac disease as their renal dysfunction progresses.",
keywords = "Heart failure, Chronic kidney disease, Blood pressure, Ejection fraction, Heart rate, Magnetic resonance, Nitric oxide, Variant genotypes",
author = "Sourabh Chand and Chue, {Colin D.} and Edwards, {Nicola C.} and James Hodson and Simmonds, {Matthew J.} and Alexander Hamilton and Gough, {Stephen C. L.} and Lorraine Harper and Steeds, {Rick P.} and Townend, {Jonathan N.} and Ferro, {Charles J.} and Richard Borrows",
year = "2015",
month = jan
day = "22",
doi = "10.1371/journal.pone.0116160",
language = "English",
volume = "10",
journal = "PLoSONE",
issn = "1932-6203",
publisher = "Public Library of Science (PLOS)",
number = "1",

}

RIS

TY - JOUR

T1 - Endothelial nitric oxide synthase single nucleotide polymorphism and left ventricular function in early chronic kidney disease

AU - Chand, Sourabh

AU - Chue, Colin D.

AU - Edwards, Nicola C.

AU - Hodson, James

AU - Simmonds, Matthew J.

AU - Hamilton, Alexander

AU - Gough, Stephen C. L.

AU - Harper, Lorraine

AU - Steeds, Rick P.

AU - Townend, Jonathan N.

AU - Ferro, Charles J.

AU - Borrows, Richard

PY - 2015/1/22

Y1 - 2015/1/22

N2 - BackgroundChronic kidney disease (CKD) is associated with accelerated cardiovascular disease and heart failure. Endothelial nitric oxide synthase (eNOS) Glu298Asp single nucleotide polymorphism (SNP) genotype has been associated with a worse phenotype amongst patients with established heart failure and in patients with progression of their renal disease. The association of a cardiac functional difference in non-dialysis CKD patients with no known previous heart failure, and eNOS gene variant is investigated.Methods140 non-dialysis CKD patients, who had cardiac magnetic resonance (CMR) imaging and tissue doppler echocardiography as part of two clinical trials, were genotyped for eNOS Glu298Asp SNP retrospectively.ResultsThe median estimated glomerular filtration rate (eGFR) was 50mls/min and left ventricular ejection fraction (LVEF) was 74% with no overt diastolic dysfunction in this cohort. There were significant differences in LVEF across eNOS genotypes with GG genotype being associated with a worse LVEF compared to other genotypes (LVEF: GG 71%, TG 76%, TT 73%, p = 0.006). After multivariate analysis, (adjusting for age, eGFR, baseline mean arterial pressure, contemporary CMR heart rate, total cholesterol, high sensitive C-reactive protein, body mass index and gender) GG genotype was associated with a worse LVEF, and increased LV end-diastolic and systolic index (p = 0.004, 0.049 and 0.009 respectively).ConclusionseNOS Glu298Asp rs1799983 polymorphism in CKD patients is associated with relevant sub-clinical cardiac remodelling as detected by CMR. This gene variant may therefore represent an important genetic biomarker, and possibly highlight pathways for intervention, in these patients who are at particular risk of worsening cardiac disease as their renal dysfunction progresses.

AB - BackgroundChronic kidney disease (CKD) is associated with accelerated cardiovascular disease and heart failure. Endothelial nitric oxide synthase (eNOS) Glu298Asp single nucleotide polymorphism (SNP) genotype has been associated with a worse phenotype amongst patients with established heart failure and in patients with progression of their renal disease. The association of a cardiac functional difference in non-dialysis CKD patients with no known previous heart failure, and eNOS gene variant is investigated.Methods140 non-dialysis CKD patients, who had cardiac magnetic resonance (CMR) imaging and tissue doppler echocardiography as part of two clinical trials, were genotyped for eNOS Glu298Asp SNP retrospectively.ResultsThe median estimated glomerular filtration rate (eGFR) was 50mls/min and left ventricular ejection fraction (LVEF) was 74% with no overt diastolic dysfunction in this cohort. There were significant differences in LVEF across eNOS genotypes with GG genotype being associated with a worse LVEF compared to other genotypes (LVEF: GG 71%, TG 76%, TT 73%, p = 0.006). After multivariate analysis, (adjusting for age, eGFR, baseline mean arterial pressure, contemporary CMR heart rate, total cholesterol, high sensitive C-reactive protein, body mass index and gender) GG genotype was associated with a worse LVEF, and increased LV end-diastolic and systolic index (p = 0.004, 0.049 and 0.009 respectively).ConclusionseNOS Glu298Asp rs1799983 polymorphism in CKD patients is associated with relevant sub-clinical cardiac remodelling as detected by CMR. This gene variant may therefore represent an important genetic biomarker, and possibly highlight pathways for intervention, in these patients who are at particular risk of worsening cardiac disease as their renal dysfunction progresses.

KW - Heart failure

KW - Chronic kidney disease

KW - Blood pressure

KW - Ejection fraction

KW - Heart rate

KW - Magnetic resonance

KW - Nitric oxide

KW - Variant genotypes

U2 - 10.1371/journal.pone.0116160

DO - 10.1371/journal.pone.0116160

M3 - Article

C2 - 25612295

VL - 10

JO - PLoSONE

JF - PLoSONE

SN - 1932-6203

IS - 1

M1 - e0116160

ER -