Genome-wide gene expression array identifies novel genes related to disease severity and excessive daytime sleepiness in patients with obstructive sleep apnea

• Published in: PloS one 2017-05, Vol.12 (5), p.e0176575-e0176575
• Main Authors: Chen, Yung-Che, Chen, Kuang-Den, Su, Mao-Chang, Chin, Chien-Hung, Chen, Chung-Jen, Liou, Chia-Wei, Chen, Ting-Wen, Chang, Ya-Chun, Huang, Kuo-Tung, Wang, Chin-Chou, Wang, Ting-Ya, Chang, Jen-Chieh, Lin, Yong-Yong, Zheng, Yi-Xin, Lin, Meng-Chih, Hsiao, Chang-Chun
• Format: Article
• Language: English
• Subjects: Actin; Acute myeloid leukemia; Adenosine; Adenosine deaminase; Adult; Angiogenesis; Anoxia; Apnea; Apoptosis; Biochemistry; Bioinformatics; Biology and Life Sciences; Biomarkers; Breathing; Cancer; Cardiovascular diseases; Cell death; Cell size; Cell survival; Chin; Comorbidity; Computer applications; Continuous positive airway pressure; Critical care; Cytochrome; Data acquisition; Data collection; Disorders of Excessive Somnolence - diagnosis; Disorders of Excessive Somnolence - etiology; Engineering; Female; Gene expression; Gene Expression Profiling; Gene Expression Regulation; Gene Regulatory Networks; Genes; Genetic aspects; Genetic Predisposition to Disease; Genome-wide association studies; Genome-Wide Association Study; Genomes; Grants; Health risks; Homology; Hospitals; Humans; Hypertension; Hypoxia; Interferon; Jaw; Kidney transplantation; Leukemia; Leukocytes, Mononuclear - metabolism; Lymphatic leukemia; Male; Medicine; Medicine and Health Sciences; Middle Aged; Modules; Mortality; Muscles; Mutation; Myeloid leukemia; Neurology; Nicotine; Oxygenation; pH effects; Physicians; Position (location); Protein expression; Proteins; Proteomics - methods; Rats; Regulations; Research and Analysis Methods; Respiration; Respiratory tract; Ribonucleic acid; Risk factors; RNA; Rodents; Science; Severity of Illness Index; Signal Transduction; Sleep; Sleep apnea; Sleep Apnea, Obstructive - complications; Sleep Apnea, Obstructive - diagnosis; Sleep Apnea, Obstructive - genetics; Sleep deprivation; Survival; Technology
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0176575

We aimed to identify novel molecular associations between chronic intermittent hypoxia with re-oxygenation and adverse consequences in obstructive sleep apnea (OSA). We analyzed gene expression profiles of peripheral blood mononuclear cells from 48 patients with sleep-disordered breathing stratified into four groups: primary snoring (PS), moderate to severe OSA (MSO), very severe OSA (VSO), and very severe OSA patients on long-term continuous positive airway pressure treatment (VSOC). Comparisons of the microarray gene expression data identified eight genes up-regulated with OSA and down-regulated with CPAP treatment, and five genes down-regulated with OSA and up-regulated with CPAP treatment. Protein expression levels of two genes related to endothelial tight junction (AMOT P130, and PLEKHH3), and three genes related to anti-or pro-apoptosis (BIRC3, ADAR1 P150, and LGALS3) were all increased in the VSO group, while AMOT P130 was further increased, and PLEKHH3, BIRC3, and ADAR1 P150 were all decreased in the VSOC group. Subgroup analyses revealed that AMOT P130 protein expression was increased in OSA patients with excessive daytime sleepiness, BIRC3 protein expression was decreased in OSA patients with hypertension, and LGALS3 protein expression was increased in OSA patients with chronic kidney disease. In vitro short-term intermittent hypoxia with re-oxygenation experiment showed immediate over-expression of ADAR1 P150. In conclusion, we identified a novel association between AMOT/PLEKHH3/BIRC3/ADAR1/LGALS3 over-expressions and high severity index in OSA patients. AMOT and GALIG may constitute an important determinant for the development of hypersomnia and kidney injury, respectively, while BIRC3 may play a protective role in the development of hypertension.