Abstract
Objective: 1) Study the association between orexin and orexin receptor genes mutations and obstructive sleep apnea syndrome. 2) Examine the effects of the identified significant mutations on the gene transcription.
Method: Prospective genetic association study. It was conducted between April 2008 and March 2010. Seventy obstructive sleep apnea patients and seventy control subjects were enrolled. Tertiary university hospital. PCR amplification followed by sequencing for Orexin Gene and TaqMan SNP Genotyping Assay for Orexin Receptor Genes was done for all participants.
Results: A novel single nucleotide deletion (IVS1+188delG) was found in one patient. An intronic mutation (rs9902709) was identified in the Orexin gene with significant difference between patients and controls when using dominant model (P = .04). A new mutation in the intron of Orexin gene was identified with significant difference between patients and controls as regards (P = .02). By examining Splicing Site Programs, this mutation showed change of the splice donor site in some of them or change of the score in others. No significant changes between patients and controls as regard Orexin receptor genes abnormalities were detected.
Conclusion: The plasma levels of Orexins have been previously evaluated in obstructive sleep apnea patients with contrary findings. This study identified two intronic mutations in the orexin gene with significant difference between patients and controls. These results suggest that orexin gene mutations may be involved in pathogenesis of obstructive sleep apnea.
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