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

Chen, Yung Che; Chen, Kuang Den; Su, Mao Chang; Chin, Chien Hung; Chen, Chung‐Jen; Liou, Chia Wei; Chen, Ting-Wen; Chang, Yuan-Chi; Huang, Kuo Tung; Wang, Chin‐Chou; Wang, Ting Ya; Chang, Jen-Chieh; Lin, Yong Yong; Zheng, Yi; Hsiao, Chang‐Chun

doi:10.1371/journal.pone.0176575

Cited by 25 publications

(17 citation statements)

References 33 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Chen et al ( 27 ) observed that alteration of the natriuretic peptide receptor 2 and its pathways was associated with the clinical phenotype of daytime sleepiness in OSA patients. In a different study from Chen et al ( 34 ), decreased expression of BIRC3 gene was associated with the development of hypertension in OSA patients. In a relatively large sample ( N = 972) of the Cleveland Family Study, Patel et al ( 30 ) showed that insertion (I)/deletion (D) polymorphisms of the angiotensin converting enzyme were associated with hypertension in OSA patients with AHI > 30.…”

Section: Resultsmentioning

confidence: 90%

See 1 more Smart Citation

Obstructive Sleep Apnea Phenotypes and Markers of Vascular Disease: A Review

et al. 2017

View full text Add to dashboard Cite

Obstructive sleep apnea (OSA) is a chronic and heterogeneous disorder that leads to early mortality, stroke, and cardiovascular disease (CVD). OSA is defined by the apnea–hypopnea index, which is an index of OSA severity that combines apneas (pauses in breathing) and hypopneas (partial obstructions in breathing) associated with hypoxemia. Yet, other sleep metrics (i.e., oxygen nadir, arousal frequency), along with clinical symptoms and molecular markers could be better predictors of stroke and CVD outcomes in OSA. The recent focus on personalized medical care introduces the possibility of a unique approach to the treatment of OSA based on its phenotypes, defined by pathophysiological mechanisms and/or clinical presentation. We summarized what is known about OSA and its phenotypes, and review the literature on factors or intermediate markers that could increase stroke risk and CVD in patients with OSA. The OSA phenotypes where divided across three different domains (1) clinical symptoms (i.e., daytime sleepiness), (2) genetic/molecular markers, and (3) experimental data-driven approach (e.g., cluster analysis). Finally, we further highlight gaps in the literature framing a research agenda.

show abstract

Section: Resultsmentioning

confidence: 90%

“…The four studies reviewed, evaluated the genetic and epigenetic markers associated with OSA clinical phenotypes and hypertension ( 27 , 30 , 34 ). Chen et al ( 27 ) observed that alteration of the natriuretic peptide receptor 2 and its pathways was associated with the clinical phenotype of daytime sleepiness in OSA patients.…”

Section: Resultsmentioning

confidence: 99%

Obstructive Sleep Apnea Phenotypes and Markers of Vascular Disease: A Review

et al. 2017

View full text Add to dashboard Cite

show abstract

“…Another key gene was the angiomotin (AMOT), which plays an important part in angiogenesis [ 72 ]. More importantly, an OSAHS genome-wide gene expression array study showed that AMOT was involved in OSAHS-related excessive daytime sleepiness by regulating a variety of endothelial cell functions [ 73 ].…”

Section: Discussionmentioning

confidence: 99%

MiRNA expression profiles in healthy OSAHS and OSAHS with arterial hypertension: potential diagnostic and early warning markers

et al. 2018

View full text Add to dashboard Cite

BackgroundObstructive sleep apnea-hypopnea syndrome (OSAHS) is prone to being complicated with various cardiovascular, cerebrovascular and metabolic conditions. OSAHS, due to its multifactorial nature, entails individualized and comprehensive treatment. So far, no well-established diagnostic criteria for the disease are available. In recent years, miRNA has been shown to be a sensitive biomarker suggestive of the progression and prognosis of many diseases. In this study, we examined some serum miRNAs in healthy OSAHS (OSAHS patients without complication) and OSAHS with arterial hypertension, with an attempt to understand the potential effects on the disease, improve the diagnosis of OSAHS and find OSAHS-related diagnostic markers.MethodsAgainst various diagnostic criteria, participants were divided into three groups: healthy OSAHS, OSAHS with arterial hypertension and healthy controls. Their serum miRNA profiles were assessed by microarray technology, and then differentially expressed miRNAs were verified by quantitative real-time PCR (qRT-PCR). The receiver operating characteristic (ROC) curves of miRNAs were constructed and the areas under the curve (AUC) were calculated. Meanwhile, the miRNAs were subjected to logistic regression analysis. The target genes were bioinformatically assessed, their functions and signaling pathways further determined and eventually an miRNA-gene network was established.ResultsAnalysis with the miRNA array exhibited that, compared with the control group, 12 differentially expressed miRNAs were found in healthy OSAHS, and 33 were found in OSAHS with arterial hypertension. The expression of miR-126-3p, let-7d-5p, miR-7641 and miR-1233-5p, miR-320b, miR-145-5p, miR-107, miR-26a-5p were validated by using qRT-PCR. Bioinformatics analysis predicted that the potential target genes of these miRNAs might be involved in metabolism, and the regulation of endothelial cells and nervous system. Moreover, the ROC analysis showed that the using miR-145-5p and let-7d-5p in combination can identify the healthy OSAHS, presence of miR-126-3p, miR-26a-5p and miR-107 was well indicative of OSAHS with arterial hypertension.ConclusionsA cluster of dysregulation miRNAs have been found to be involved in the development of OSAHS patients. Moreover, these miRNAs might be used to be potential diagnostic and early warning markers.

show abstract

“…In fact, Wu et al 27 identified, after genotype analysis of data generated from dogs conditioned to high altitude, five genes related to hypoxia-adaptation signatures on the X chromosome, among which was the AMOT gene. At the clinical stage, an increase of AMOT p130 expression has been reported in a group of patients suffering from obstructive sleep apnoea 28 , confirming the implication of AMOT in chronic intermittent hypoxia with re-oxygenation. Overexpression of p80 and p130 isoforms in this context of revascularisation confirms previous data describing the expression profile of each isoform over the different steps of angiogenesis 29 .…”

Section: Discussionmentioning

confidence: 56%

Early prediction of revascularisation by angiomotin-targeting positron emission tomography

Moyon¹,

Garrigue²,

Balasse³

et al. 2018

Theranostics

View full text Add to dashboard Cite

This study aimed to develop a PET imaging agent of angiomotin (AMOT) expression, a potential biomarker of functional tissue regeneration in post-ischaemic conditions.Methods: Hindlimb ischaemia was induced by ligature and resection of the right femoral artery in mice, and clinical score and limb perfusion were evaluated up to 30 days after surgery. AMOT expression was evaluated by histology and Western blot analysis. NODAGA-conjugates of AMOT ligand, sCD146, were designed, synthesised and radiolabelled with gallium-68. 68Ga-sCD146 microPET/CT imaging was performed from day 1 to day 30 after ischaemia. 68Ga-sCD146 specificity for AMOT was evaluated by autoradiography.Results: Immunohistochemistry showed a significant endothelial overexpression of AMOT from day 5 up to day 10 in the ischaemic hindlimb. 68Ga-sCD146 PET signal intensity correlated significantly with AMOT immunohistochemistry evaluation. 68Ga-sCD146 PET imaging showed a significant uptake in the ischaemic hindlimb from day 2 to day 15, peaking on day 5 (ipsi/contralateral ratio = 2.4 ± 1.3, P = 0.0005) and significantly decreased after pharmacological blocking (62.57 ± 11% decrease in PET signal P = 0.032). Finally, we observed a significant correlation between day 5 68Ga-sCD146 PET signal intensity and clinical recovery (day 28) or hindlimb perfusion recovery (day 30).Conclusions: This work reports for the first time an early and sustained increase in AMOT expression after hindlimb ischaemia in mice. We therefore developed an AMOT-targeting imaging agent, 68Ga-sCD146, and showed its specific uptake up to 21 days after ischaemic hindlimb using microPET imaging. Correlation of early post-ischaemic PET signal with both delayed perfusion recovery and clinical outcome allows us to postulate that 68Ga-sCD146 represents a promising radiotracer for tissue angiogenesis assessment.

show abstract

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

Cited by 25 publications

References 33 publications

Obstructive Sleep Apnea Phenotypes and Markers of Vascular Disease: A Review

Obstructive Sleep Apnea Phenotypes and Markers of Vascular Disease: A Review

MiRNA expression profiles in healthy OSAHS and OSAHS with arterial hypertension: potential diagnostic and early warning markers

Early prediction of revascularisation by angiomotin-targeting positron emission tomography

Contact Info

Product

Resources

About