Publication:
Genetic variance in Nitric Oxide Synthase and Endothelin Genes among children with and without Endothelial Dysfunction

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Issued Date

2013

Resource Type

Article

File Type

application/pdf

ISSN

14795876

DOI

10.1186/1479-5876-11-227

Other identifier(s)

2-s2.0-84884517687

Rights Holder(s)

Scopus

Bibliographic Citation

Journal of Translational Medicine. Vol 11, No.1 (2013), p.-

Suggested Citation

Chatsuriyawong S., Gozal D., Kheirandish-Gozal L., Bhattacharjee R., Khalyfa A.A., Wang Y., Hakonarson H., Keating B., Sukhumsirichart W., Khalyfa A. Genetic variance in Nitric Oxide Synthase and Endothelin Genes among children with and without Endothelial Dysfunction. Journal of Translational Medicine. Vol 11, No.1 (2013), p.-. doi:10.1186/1479-5876-11-227 Retrieved from: https://hdl.handle.net/20.500.14740/6549

Title

Genetic variance in Nitric Oxide Synthase and Endothelin Genes among children with and without Endothelial Dysfunction

Author(s)

Chatsuriyawong S.
 Gozal D.
 Kheirandish-Gozal L.
 Bhattacharjee R.
 Khalyfa A.A.
 Wang Y.
 Hakonarson H.
 Keating B.
 Sukhumsirichart W.
 Khalyfa A.

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.

Subject(s)

C reactive protein
 Endothelial nitric oxide synthase
 Endothelin
 Endothelin 1
 Endothelin 2
 Endothelin 3
 Endothelin A receptor
 Endothelin B receptor
 Genomic DNA
 Glucose
 Inducible nitric oxide synthase
 Insulin
 Lipid
 Neuronal nitric oxide synthase
 Nitric oxide synthase
 Article
 Cardiovascular risk
 Child
 Cohort analysis
 Computer program
 Controlled study
 Edn1 gene
 Endothelial dysfunction
 Endothelin gene
 Enzyme linked immunosorbent assay
 Female
 Gene linkage disequilibrium
 Genetic association
 Genetic risk
 Genetic variability
 Genotype phenotype correlation
 Glucose blood level
 Human
 Insulin blood level
 Lipid blood level
 Major clinical study
 Male
 Molecular pathology
 Mutation rate
 Nitric oxide synthase gene
 NOS1 gene
 Obesity
 Preschool child
 Prospective study
 Protein blood level
 Reverse transcription polymerase chain reaction
 Risk factor
 School child
 Single nucleotide polymorphism
 Alleles
 Child
 Child, Preschool
 Cohort Studies
 Demography
 Endothelins
 Endothelium, Vascular
 Female
 Gene Expression Regulation
 Gene Frequency
 Genetic Association Studies
 Haplotypes
 Humans
 Linkage Disequilibrium
 Male
 Nitric Oxide Synthase
 Phenotype
 Polymorphism, Single Nucleotide
 Reproducibility of Results
 Reverse Transcriptase Polymerase Chain Reaction

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URI

https://hdl.handle.net/20.500.14740/6549

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Scopus: Year 1983-2021

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