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Title: Genetic variance in Nitric Oxide Synthase and Endothelin Genes among children with and without Endothelial Dysfunction
Authors: Chatsuriyawong S.
Gozal D.
Kheirandish-Gozal L.
Bhattacharjee R.
Khalyfa A.A.
Wang Y.
Hakonarson H.
Keating B.
Sukhumsirichart W.
Khalyfa A.
Keywords: C reactive protein
endothelial nitric oxide synthase
endothelin 1
endothelin 2
endothelin 3
endothelin A receptor
endothelin B receptor
genomic DNA
inducible nitric oxide synthase
neuronal nitric oxide synthase
nitric oxide synthase
cardiovascular risk
cohort analysis
computer program
controlled study
Edn1 gene
endothelial dysfunction
endothelin gene
enzyme linked immunosorbent assay
gene linkage disequilibrium
genetic association
genetic risk
genetic variability
genotype phenotype correlation
glucose blood level
insulin blood level
lipid blood level
major clinical study
molecular pathology
mutation rate
nitric oxide synthase gene
NOS1 gene
preschool child
prospective study
protein blood level
reverse transcription polymerase chain reaction
risk factor
school child
single nucleotide polymorphism
Child, Preschool
Cohort Studies
Endothelium, Vascular
Gene Expression Regulation
Gene Frequency
Genetic Association Studies
Linkage Disequilibrium
Nitric Oxide Synthase
Polymorphism, Single Nucleotide
Reproducibility of Results
Reverse Transcriptase Polymerase Chain Reaction
Issue Date: 2013
Abstract: Background: The presence of endothelial dysfunction (ED) constitutes an early risk factor for cardiovascular disease (CVD) in children. Nitric oxide (NO) and endothelin (EDN) are generated in endothelial cells and are critical regulators of vascular function, with ED resulting from an imbalance between these two molecules. We hypothesized that genetic variants in NO synthase and EDN isoforms and its receptors (EDNRA and EDNRB) may account for a proportion of the risk for ED in developing children.Methods: Consecutive children (ages 5-10 years) were prospectively recruited from the community. Time to peak post-occlusive reperfusion (Tmax) was considered as the indicator of either normal endothelial function (NEF; Tmax < 45 sec) or ED (Tmax ≥ 45 sec). Lipid profiles, high sensitivity C-reactive protein (hsCRP), fasting glucose and insulin were assayed using ELISA. Genomic DNA from peripheral blood was extracted and genotyped for NOS1 (209 SNPs), NOS2 (122 SNPs), NOS3 (50 SNPs), EDN1 (43 SNPs), EDN2 (48 SNPs), EDN3 (14 SNPs), EDNRA (27 SNPs), and EDNRB (23 SNPs) using a custom SNPs array. Linkage disequilibrium was analyzed using Haploview version 4.2 software.Results: The relative frequencies of SNPs were evaluated in 122 children, 84 with NEF and 38 with ED. The frequencies of NOS1 (11 SNPs), and EDN1 (2 SNPs) were differentially distributed between NEF vs. ED, and no significant differences emerged for all other genes. Significant SNPs for NOS1 and EDN1 SNPs were further validated with RT-PCR.Conclusions: Genetic variants in the NOS1 and EDN1 genes appear to account for important components of the variance in endothelial function, particularly when concurrent risk factors such as obesity exist. Thus, analysis of genotype-phenotype interactions in children at risk for ED will be critical for more accurate formulation of categorical CVD risk estimates. © 2013 Chatsuriyawong et al.; licensee BioMed Central Ltd.
ISSN: 14795876
Appears in Collections:Scopus 1983-2021

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