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En Face Detection of Nitric Oxide and Superoxide in Endothelial Layer of Intact Arteries
Published on: February 25, 2016
Genetic variance in nitric oxide synthase and endothelin genes among children with and without endothelial
Siriporn Chatsuriyawong1, David Gozal, Leila Kheirandish-Gozal
1Department of Pediatrics, Comer Children's Hospital, Pritzker School of Medicine, Biological Sciences Division, The University of Chicago, 900 E, 57th Street, KCBD, 4112, Chicago 60637, IL, USA. akhalyfa@uchicago.edu.
Insights
Genetic variants in NOS1 and EDN1 genes are linked to endothelial dysfunction (ED) in children. Understanding these genetic factors is crucial for assessing cardiovascular disease (CVD) risk in pediatric populations.
Area of Science:
- Pediatric cardiovascular health
- Genetics and molecular biology
- Vascular endothelial function
Background:
- Endothelial dysfunction (ED) is an early indicator of cardiovascular disease (CVD) risk in children.
- Imbalance between nitric oxide (NO) and endothelin (EDN) contributes to ED.
- Genetic variations in NO and EDN pathways may influence ED risk in children.
Purpose of the Study:
- To investigate the association between genetic variants in nitric oxide synthase (NOS) and endothelin (EDN) genes and ED in children.
- To determine if specific gene polymorphisms correlate with endothelial function in pediatric subjects.
Main Methods:
- Prospective recruitment of children aged 5-10 years.
- Assessed endothelial function using time to peak post-occlusive reperfusion (Tmax).
- Genotyped multiple single nucleotide polymorphisms (SNPs) in NOS1, NOS2, NOS3, EDN1, EDN2, EDN3, EDNRA, and EDNRB genes.
Main Results:
- Evaluated SNP frequencies in 122 children (84 with normal endothelial function, 38 with ED).
- Found differential distribution of specific SNPs in NOS1 and EDN1 genes between children with normal endothelial function and those with ED.
- Validated significant NOS1 and EDN1 SNPs using RT-PCR.
Conclusions:
- Genetic variants in NOS1 and EDN1 genes contribute to the variability in endothelial function in children.
- These genetic factors are particularly relevant when other risk factors like obesity are present.
- Genotype-phenotype interaction analysis is essential for accurate CVD risk estimation in at-risk children.
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.
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