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

Chand, S. and Chue, C. D. and Edwards, N. C. and Hodson, J. and Simmonds, M. J. and Hamilton, A. and Gough, S. C. L. and Harper, L. and Steeds, R. P. and Townend, J. N. and Ferro, C. J. and Borrows, R. (2015) Endothelial nitric oxide synthase single nucleotide polymorphism and left ventricular function in early chronic kidney disease. PLoS ONE, 10 (1). ISSN 1932-6203

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Abstract

Chronic 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. Methods 140 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. Results The 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). Conclusions eNOS 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. © 2015 Chand et al.

Keywords:C reactive protein, cholesterol, endothelial nitric oxide synthase, adult, aged, Article, body mass, cardiovascular magnetic resonance, cholesterol blood level, chronic kidney disease, cohort analysis, controlled study, disease association, female, gender, genetic variability, genotype, glomerulus filtration rate, heart left ventricle ejection fraction, heart left ventricle function, human, major clinical study, male, mean arterial pressure, retrospective study, single nucleotide polymorphism, tissue Doppler imaging, JCOpen
Subjects:C Biological Sciences > C420 Human Genetics
Divisions:College of Science > School of Life Sciences
ID Code:22592
Deposited On:16 Mar 2016 14:50

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