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

BMC Medical Genomics

Abdelnaby Khalyfa²  Wasana Sukhumsirichart¹  Yang Wang²  Ahamed A Khalyfa²  Rakesh Bhattacharjee²  Leila Kheirandish-Gozal²  David Gozal²  Siriporn Chatsuriyawong¹ 

[1] Department of Biochemistry, Faculty of Medicine, Srinakharinwirot University, Sukhumvit 23, Bangkok 10110, Thailand;Department of Pediatrics, Comer Children's Hospital, Pritzker School of Medicine, Biological Sciences Division, The University of Chicago, 900 E, 57th Street, KCBD, 4112, Chicago, IL 60637, USA

关键词: Polymorphisms;    SNP;    Endothelin (EDN);    Nitric oxide synthase (NOS);    OSA;    Children;   

Others  :  1092245
DOI  :  10.1186/1755-8794-6-29

 received in 2013-05-27, accepted in 2013-08-29,  发布年份 2013

【 摘 要 】

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.

【 授权许可】

   
2013 Chatsuriyawong et al.; licensee BioMed Central Ltd.

【 图 表 】

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