Sleep Medicine
Volume 10, Issue 1 , Pages 75-86, January 2009

Genome-wide gene expression profiling in children with non-obese obstructive sleep apnea☆

  • Abdelnaby Khalyfa

      Affiliations

    • Kosair Children’s Hospital Research Institute, Department of Pediatrics, University of Louisville, 570 South Preston Street, Suite 204, Louisville, KY 40202, USA
    • ,
  • Oscar Sans Capdevila

      Affiliations

    • Division of Pediatric Sleep Medicine, Department of Pediatrics, University of Louisville, 571 S. Floyd Street, Suite 439, Louisville, KY 40202, USA
    • ,
  • Mohamed O. Buazza

      Affiliations

    • Kosair Children’s Hospital Research Institute, Department of Pediatrics, University of Louisville, 570 South Preston Street, Suite 204, Louisville, KY 40202, USA
    • ,
  • Laura D. Serpero

      Affiliations

    • Kosair Children’s Hospital Research Institute, Department of Pediatrics, University of Louisville, 570 South Preston Street, Suite 204, Louisville, KY 40202, USA
    • ,
  • Leila Kheirandish-Gozal

      Affiliations

    • Kosair Children’s Hospital Research Institute, Department of Pediatrics, University of Louisville, 570 South Preston Street, Suite 204, Louisville, KY 40202, USA
    • Division of Pediatric Sleep Medicine, Department of Pediatrics, University of Louisville, 571 S. Floyd Street, Suite 439, Louisville, KY 40202, USA
    • ,
  • David Gozal

      Affiliations

    • Kosair Children’s Hospital Research Institute, Department of Pediatrics, University of Louisville, 570 South Preston Street, Suite 204, Louisville, KY 40202, USA
    • Division of Pediatric Sleep Medicine, Department of Pediatrics, University of Louisville, 571 S. Floyd Street, Suite 439, Louisville, KY 40202, USA
    • Corresponding Author InformationCorresponding author. Address: Kosair Children’s Hospital Research Institute, Department of Pediatrics, University of Louisville, 570 South Preston Street, Suite 204, Louisville, KY 40202, USA. Tel.: +1 502 852 2323; fax: +1 502 852 2215.

Received 13 September 2007; received in revised form 31 October 2007; accepted 3 November 2007.

Abstract 

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.

Methods and 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.

Keywords: Obstructive sleep apnea (OSA), Microarray, Genome-wide array, Gene expression profiles, Inflammation, Adenotonsillar hypertrophy

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☆ Funding sources: A.K. is supported by University of Louisville Institutional Research Grant E0606. D.G. is supported by NIH Grants HL-65270 and HL-83075, The Children’s Foundation Endowment for Sleep Research, and by the Commonwealth of Kentucky Challenge for Excellence Trust Fund. L.K.G. is supported by a grant from the National Space Agency (NNJ05HF 06G).

PII: S1389-9457(07)00375-9

doi:10.1016/j.sleep.2007.11.006

Sleep Medicine
Volume 10, Issue 1 , Pages 75-86, January 2009

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