Publication:
Polymorphisms in nitric oxide synthase and endothelin genes among children with obstructive sleep apnea

0
0

Issued Date

2013

Resource Type

Article

File Type

application/pdf

ISSN

17558794

DOI

10.1186/1755-8794-6-29

Other identifier(s)

2-s2.0-84883539642

Rights Holder(s)

Scopus

Bibliographic Citation

BMC Medical Genomics. Vol 6, No.1 (2013), p.-

Suggested Citation

Chatsuriyawong S., Gozal D., Kheirandish-Gozal L., Bhattacharjee R., Khalyfa A.A., Wang Y., Sukhumsirichart W., Khalyfa A. Polymorphisms in nitric oxide synthase and endothelin genes among children with obstructive sleep apnea. BMC Medical Genomics. Vol 6, No.1 (2013), p.-. doi:10.1186/1755-8794-6-29 Retrieved from: https://hdl.handle.net/20.500.14740/6552

Title

Polymorphisms in nitric oxide synthase and endothelin genes among children with obstructive sleep apnea

Author(s)

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

Abstract

Background: Obstructive sleep apnea (OSA) is associated with adverse and interdependent cognitive and cardiovascular consequences. Increasing evidence suggests that nitric oxide synthase (NOS) and endothelin family (EDN) genes underlie mechanistic aspects of OSA-associated morbidities. We aimed to identify single nucleotide polymorphisms (SNPs) in the NOS family (3 isoforms), and EDN family (3 isoforms) to identify potential associations of these SNPs in children with OSA. Methods. A pediatric community cohort (ages 5-10 years) enriched for snoring underwent overnight polysomnographic (NPSG) and a fasting morning blood draw. The diagnostic criteria for OSA were an obstructive apnea-hypopnea Index (AHI) >2/h total sleep time (TST), snoring during the night, and a nadir oxyhemoglobin saturation <92%. Control children were defined as non-snoring children with AHI <2/h TST (NOSA). Endothelial function was assessed using a modified post-occlusive hyperemic test. The time to peak reperfusion (Tmax) was considered as the indicator for normal endothelial function (NEF; Tmax<45 sec), or ED (Tmax≥45 sec). Genomic DNA from peripheral blood was extracted and allelic frequencies were assessed for, NOS1 (209 SNPs), NOS2 (122 SNPs), NOS3 (50 SNPs), EDN1 (43 SNPs), EDN2 (48 SNPs), EDN3 (14 SNPs), endothelin receptor A, EDNRA, (27 SNPs), and endothelin receptor B, EDNRB (23 SNPs) using a custom SNPs array. The relative frequencies of NOS-1,-2, and -3, and EDN-1,-2,-3,-EDNRA, and-EDNRB genotypes were evaluated in 608 subjects [128 with OSA, and 480 without OSA (NOSA)]. Furthermore, subjects with OSA were divided into 2 subgroups: OSA with normal endothelial function (OSA-NEF), and OSA with endothelial dysfunction (OSA-ED). Linkage disequilibrium was analyzed using Haploview version 4.2 software. Results: For NOSA vs. OSA groups, 15 differentially distributed SNPs for NOS1 gene, and 1 SNP for NOS3 emerged, while 4 SNPs for EDN1 and 1 SNP for both EDN2 and EDN3 were identified. However, in the smaller sub-group for whom endothelial function was available, none of the significant SNPs was retained due to lack of statistical power. Conclusions: Differences in the distribution of polymorphisms among NOS and EDN gene families suggest that these SNPs could play a contributory role in the pathophysiology and risk of OSA-induced cardiovascular morbidity. Thus, analysis of genotype-phenotype interactions in children with OSA may assist in the formulation of categorical risk estimates. © 2013 Chatsuriyawong et al.; licensee BioMed Central Ltd.

Subject(s)

Endothelial nitric oxide synthase
 Endothelin
 Endothelin receptor
 Genomic DNA
 Inducible nitric oxide synthase
 Isoprotein
 Neuronal nitric oxide synthase
 Nitric oxide synthase
 Oxyhemoglobin
 Protein EDNRA
 Protein EDNRB
 Unclassified drug
 Apnea hypopnea index
 Article
 Blood analysis
 Child
 Cohort analysis
 Computer program
 Controlled study
 DNA extraction
 Edn1 gene
 EDN2 gene
 EDN3 gene
 EDNRA gene
 EDNRB gene
 Endothelial dysfunction
 Female
 Gene
 Gene frequency
 Gene linkage disequilibrium
 Genetic identification
 Genotype
 Human
 Major clinical study
 Male
 Multigene family
 NOS1 gene
 Nos2 gene
 NOS3 gene
 Oxygen saturation
 Polysomnography
 Preschool child
 Priority journal
 Protein assembly
 Protein localization
 School child
 Single nucleotide polymorphism
 Sleep disordered breathing
 Sleep time
 Snoring
 Time to maximum plasma concentration
 Osa
 Child
 Child, Preschool
 Endothelins
 Female
 Gene Frequency
 Genetic Predisposition to Disease
 Humans
 Male
 Nitric Oxide Synthase
 Polymorphism, Single Nucleotide
 Polysomnography
 Sleep Apnea, Obstructive

View online Resources

Research Projects

Organizational Units

Journal Issue

URI

https://hdl.handle.net/20.500.14740/6552

Collections

Scopus: Year 1983-2021

Endorsement

Review

Supplemented By

Referenced By