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Genomics of Sleep-disordered Breathing

Division of Pulmonary and Critical Care Medicine, The Johns Hopkins Medical School, Baltimore Maryland; and Division of Pulmonary, Allergy, and Critical Care Medicine, University of Pittsburgh Medical School, Pittsburgh, Pennsylvania

Correspondence and requests for reprints should be addressed to Christopher P. O'Donnell, Ph.D., Division of Pulmonary, Allergy, and Critical Care Medicine, University of Pittsburgh Medical School, NW 628 UPMC Montefiore, 3459 Fifth Avenue, Pittsburgh, PA 15213. E-mail: odonnellcp{at}upmc.edu

ABSTRACT

The technologies of genomics and proteomics are powerful tools for discovering novel gene and protein expression responses to disease. Considerable evidence indicates that a genetic basis exists to the causes of sleep-disordered breathing, in particular its most common form of obstructive sleep apnea (OSA), which is characterized by periods of intermittent hypoxia and disrupted sleep. However, the genetic contribution to the pathogenesis of OSA has largely been determined using traditional genetic approaches of family, twin, and linkage studies in clinical populations and quantitative trait loci and targeted gene procedures in animal models of OSA. In contrast to the pathogenesis of OSA, the consequences or sequelae of OSA are highly amenable to genomic and proteomic approaches. Animal studies have assessed changes in gene and protein expression in multiple organ systems in response to intermittent hypoxia and sleep deprivation and uncovered novel gene activation paradigms. The first tentative steps have been made toward applying proteomic analyses of blood and urine from patients with OSA as a potential screening tool for diagnosis in the clinical setting. It is anticipated that genomic and proteomic technologies will become increasingly used in the area of OSA with the unprecedented access to tissue in procedures such as bariatric surgery. OSA represents a severe insult to the oxygenation of tissues and the homeostasis of sleep, and genomic and proteomic approaches hold promise for defining previously unexplored mechanisms and pathways that lead to downstream pathologies, including hypertension, insulin resistance, and neurocognitive dysfunction.

Key Words: hypertension • insulin resistance • intermittent hypoxia • obstructive sleep apnea • proteomics

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