Genome-wide gene expression profiling in children with non-obese obstructive sleep apnea.
BACKGROUND
Obstructive sleep apnea (OSA) is a multi-factorial and highly prevalent disorder in which both genetic and environmental factors may be involved. If left untreated, OSA may lead to significant cardiovascular and neurocognitive and behavioral morbidities. We hypothesized that pediatric OSA would lead to altered gene expression in circulating leukocytes.


RESULTS
Oligonucleotide-based microarray technology was used to identify mRNAs that may be differentially regulated in non-obese children with polysomnographically-established OSA compared to matched control children. Total morning blood RNA from 40 children (20 OSA and 20 controls) was extracted, labeled, and hybridized onto independent oligonucleotide-based microarrays. Of the 44,000 transcripts, 1217 transcripts were differentially expressed in OSA (p-value <0.05), with 68 transcripts (38 RefSeq accession numbers, 30 ESTs) fulfilling high stringency criteria. False Discovery rate (FDR) was used to determine the significance-difference of OSA vs. normal samples. Microarray data were further validated using quantitative RT-PCR techniques. Biological pathways pertinent to the differentially expressed genes were explored and revealed prominent involvement of inflammatory pathways.


CONCLUSIONS
RNA derived from peripheral leukocytes confirms the presence of altered expression of functionally relevant gene clusters in pediatric OSA. Large-scale genomic approaches may provide further insights into adaptive and end-organ injury related mechanisms in the context of OSA in children.
Khalyfa
Abdelnaby
A
Kosair Children's Hospital Research Institute, Department of Pediatrics, University of Louisville, 570 South Preston Street, Suite 204, Louisville, KY 40202, USA.
Capdevila
Oscar Sans
OS
Buazza
Mohamed O
MO
Serpero
Laura D
LD
Kheirandish-Gozal
Leila
L
Gozal
David
D
D000234:Adenoids / Q000473:pathology; D001835:Body Weight; D002648:Child; D005260:Female; D020869:Gene Expression Profiling; D023281:Genomics; D006801:Humans; D006984:Hypertrophy; D008297:Male; D020411:Oligonucleotide Array Sequence Analysis; D014066:Palatine Tonsil / Q000473:pathology; D017286:Polysomnography; D020133:Reverse Transcriptase Polymerase Chain Reaction; D020181:Sleep Apnea, Obstructive / Q000235:genetics* / Q000473:pathology; D014069:Tonsillitis / Q000235:genetics* / Q000473:pathology