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Integrative analysis of key candidate genes and signaling pathways in acute coronary syndrome related to obstructive sleep apnea by bioinformatics.

ABSTRACT: Although obstructive sleep apnea (OSA) has been clinically reported to be associated with acute coronary syndrome (ACS), the pathogenesis between the two is unclear. Herein, we analyzed and screened out the prospective molecular marker. To explore the candidate genes, as well as signaling cascades involved in ACS related to OSA, we extracted the integrated differentially expressed genes (DEGs) from the intersection of genes from the Gene Expression Omnibus (GEO) cohorts and text mining, followed by enrichment of the matching cell signal cascade through DAVID analysis. Moreover, the MCODE of Cytoscape software was employed to uncover the protein-protein interaction (PPI) network and the matching hub gene. A total of 17 and 56 integrated human DEGs in unstable angina (UA) and myocardial infarction (MI) group associated with OSAs that met the criteria of |log2 fold change (FC)|≥ 1, adjusted P < 0.05, respectively, were uncovered. After PPI network construction, the top five hub genes associated with UA were extracted, including APP, MAPK3, MMP9, CD40 and CD40LG, whereas those associated with MI were PPARG, MAPK1, MMP9, AGT, and TGFB1. The establishment of the aforementioned candidate key genes, as well as the enriched signaling cascades, provides promising molecular marker for OSA-related ACS, which will to provide a certain predictive value for the occurrence of ACS in OSA patients in the future.

SUBMITTER: Shi Y

PROVIDER: S-EPMC8266822 | biostudies-literature | 2021 Jul

REPOSITORIES: biostudies-literature

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Integrative analysis of key candidate genes and signaling pathways in acute coronary syndrome related to obstructive sleep apnea by bioinformatics.

Shi Yanxi Y Jiang Zhengye Z Jiang Liqin L Xu Jianjiang J

Scientific reports 20210708 1

Although obstructive sleep apnea (OSA) has been clinically reported to be associated with acute coronary syndrome (ACS), the pathogenesis between the two is unclear. Herein, we analyzed and screened out the prospective molecular marker. To explore the candidate genes, as well as signaling cascades involved in ACS related to OSA, we extracted the integrated differentially expressed genes (DEGs) from the intersection of genes from the Gene Expression Omnibus (GEO) cohorts and text mining, followed ...[more]

PMID: 34239024

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Project description:Carpal tunnel syndrome (CTS) is the most common entrapment neuropathy of the upper extremity. It is usually associated with the compression of the median nerve in the median groove. Because the main symptoms of CTS pain and numbness worsen at night, sleep disorders in CTS patients and the impact of preferred sleeping position on CTS development have been formerly studied. However, to the best of our knowledge, this is the first study assessing the frequency of CTS in obstructive sleep apnea (OSA) patients. This study aimed to determine the frequency of CTS in OSA patients and evaluate the causative relation between the two diseases.Records of individuals who were admitted to our sleep laboratory were retrospectively scanned. Eighty patients who were diagnosed with OSA and did not have comorbidities that might cause OSA (e.g., diabetes mellitus, hypothyroiditis, rheumatic diseases, and cervical radiculopathy) were included in the study along with 80 healthy controls who matched for age, sex, and BMI of OSA patients. To maintain observer blindness, patients were not questioned regarding their symptoms or the clinical data that would be used in the study. All participants underwent nerve conduction studies. Those who were diagnosed with CTS were questioned regarding CTS symptoms and the preferred sleeping position. Subsequently, patients were given the Boston CTS questionnaire.CTS frequency in OSA patients was found to be 27.5%. There was no significant relation between preferred sleeping position or being a manual worker and having CTS.CTS frequency in OSA patients is significantly higher than that in healthy individuals. In contrast to previous studies that have been performed in the absence of polysomnographic and electrophysiological data, in our study biomechanical factors were not associated with CTS presence. Therefore, we conclude that intermittent hypoxemia is the main etiological factor for CTS in OSA patients. Inflammation may be a common factor for etiopathogenesis for both diseases, but this hypothesis needs further investigation.

Project description:Background The aim of this prospective study was to determine the impact of elevated ANGPTL3 (angiopoietin-like protein 3) on cardiovascular events (CVEs) following acute coronary syndrome (ACS) in patients with or without obstructive sleep apnea (OSA). Methods and Results A total of 1174 patients with ACS underwent successful percutaneous coronary intervention were included in this prospective cohort study (NCT03362385). Patients were categorized according to the apnea-hypopnea index (≥15 events/h, OSA) and further classified by ANGPTL3 levels. We analyzed the incidence of CVEs in patients with ACS according to the status of OSA and ANGPTL3. During a median of 3.1 years of follow-up, 217 (18.48%) CVEs occurred. The patients with ACS with OSA had higher ANGPTL3 levels than those without OSA (30.4 [20.9-43.2] versus 27.80 [19.1-41.5] ng/mL; P<0.001). In all patients with ACS, 29≤ANGPTL3<42 mg/dL and ANGPTL3≥42 mg/dL were associated with an increased risk of CVEs with hazard ratios (HRs) of 1.555 (95% CI, 1.010-2.498) and 2.489 (95% CI 1.613-3.840), respectively. When the status of OSA or not was incorporated in stratifying factors, 29≤ANGPTL3<42 mg/dL and ANGPTL3≥42 mg/dL were associated with a significantly higher risk of CVEs in patients with ACS with OSA (HR, 1.916 [95% CI, 1.019-3.601] and HR, 2.692 [95% CI, 1.379-4.503]) but not without OSA. Moreover, adding ANGPTL3 to the Cox model increased C-statistic values by 0.035 and 0.029 in the OSA group and all patients with ACS, respectively, but was not statistically improved in patients with ACS without OSA. Conclusions In conclusion, our study demonstrates a predictive impact of plasma ANGPTL3 on cardiovascular risk in patients with ACS, especially in patients with ACS with OSA. It might be of clinical value in refining risk stratification and tailoring treatment of patients with ACS and OSA. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT03362385.

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Integrative analysis of key candidate genes and signaling pathways in acute coronary syndrome related to obstructive sleep apnea by bioinformatics.

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Integrative analysis of key candidate genes and signaling pathways in acute coronary syndrome related to obstructive sleep apnea by bioinformatics.

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