Functional polymorphisms in the promoter region of MMP-2 and MMP-9 and susceptibility to obstructive sleep apnea.
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ABSTRACT:
SUBMITTER: Cao C
PROVIDER: S-EPMC4354173 | biostudies-literature | 2015
REPOSITORIES: biostudies-literature
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Functional polymorphisms in the promoter region of MMP-2 and MMP-9 and susceptibility to obstructive sleep apnea.
Cao Chao C Wu Bin B Wu Yanping Y Yu Yiming Y Ma Hongying H Sun Shifang S Zhang Qiaoli Q Ding Qunli Q Chen Li L Deng Zaichun Z
Scientific reports 20150310
Genetic susceptibility to obstructive sleep apnea (OSA) has been a research focus in the scientific community in the past few years. In this study, we recruited 375 subjects to investigate whether functional polymorphisms in the promoter region of matrix metalloproteinase (MMP)-2 (-1306C/T) and MMP-9 (-1562C/T) increased susceptibility to OSA. Our study showed no significant association between MMP-2 -1306C/T polymorphism and risk of OSA (T vs. C: OR = 1.01, 95% CI = 0.67-1.52; P = 0.97). Compar ...[more]
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Project description:Rationale: Obstructive sleep apnea (OSA) has been associated with metabolic dysregulation and systemic inflammation. This may be due to pathophysiologic effects of OSA on visceral adipose tissue. We sought to assess the transcriptional consequences of OSA on adipocytes by utilizing pathway-focused analyses. Methods: Patients scheduled to undergo ventral hernia repair surgery were recruited to wear a portable home sleep monitor for two nights prior to surgery. Visceral fat biopsies were obtained intra-operatively. RNA was extracted and whole-genome expression profiling was performed. Gene Set Enrichment Analysis (GSEA) was used to identify curated gene sets that were differentially enriched in OSA subjects. Network analysis was applied to a select set of highly enriched pathways. Results: 10 patients with OSA and 8 control subjects were recruited. There were no differences in age, gender, body mass index between the two groups, but the OSA subjects had a significantly higher respiratory disturbance index (19.2 vs. 0.6, P-value 0.05) and worse hypoxemia (minimum oxygen saturation 79.7% vs. 87.8%, P-value < 0.001). GSEA identified a number of gene sets up-regulated in adipose tissue of OSA patients including the pro-inflammatory NF-M-NM-:B pathway and the proteolytic ubiquitin/proteasome module. A critical metabolic pathway, the peroxisome proliferator-activated receptor (PPAR), was down-regulated in subjects with OSA. Network analysis linked members of these modules together and identified regulatory hubs. Conclusions: OSA is associated with alterations in visceral fat gene expression. Pathway-based network analysis highlighted perturbations in several key pathways whose coordinated interactions may contribute to the metabolic dysregulation observed in this complex disorder. Total RNA from visceral fat of 18 subjects (10 OSA, 8 Control) was hybridized to 18 Affymetrix Genechip Human Gene 1.0 ST microarrays.
2012-09-01 | E-GEOD-38792 | biostudies-arrayexpress
Project description:Rationale: Obstructive sleep apnea (OSA) has been associated with metabolic dysregulation and systemic inflammation. This may be due to pathophysiologic effects of OSA on visceral adipose tissue. We sought to assess the transcriptional consequences of OSA on adipocytes by utilizing pathway-focused analyses. Methods: Patients scheduled to undergo ventral hernia repair surgery were recruited to wear a portable home sleep monitor for two nights prior to surgery. Visceral fat biopsies were obtained intra-operatively. RNA was extracted and whole-genome expression profiling was performed. Gene Set Enrichment Analysis (GSEA) was used to identify curated gene sets that were differentially enriched in OSA subjects. Network analysis was applied to a select set of highly enriched pathways. Results: 10 patients with OSA and 8 control subjects were recruited. There were no differences in age, gender, body mass index between the two groups, but the OSA subjects had a significantly higher respiratory disturbance index (19.2 vs. 0.6, P-value 0.05) and worse hypoxemia (minimum oxygen saturation 79.7% vs. 87.8%, P-value < 0.001). GSEA identified a number of gene sets up-regulated in adipose tissue of OSA patients including the pro-inflammatory NF-κB pathway and the proteolytic ubiquitin/proteasome module. A critical metabolic pathway, the peroxisome proliferator-activated receptor (PPAR), was down-regulated in subjects with OSA. Network analysis linked members of these modules together and identified regulatory hubs. Conclusions: OSA is associated with alterations in visceral fat gene expression. Pathway-based network analysis highlighted perturbations in several key pathways whose coordinated interactions may contribute to the metabolic dysregulation observed in this complex disorder.
2012-09-01 | GSE38792 | GEO
Project description:At present, variants of the 5-hydroxytryptamine receptor 2A (5-HTR2A) and interleukin-6 (IL-6) genes may be susceptible markers to develop for obstructive sleep apnea-hypopnea syndrome (OSAHS). Therefore, the aim of the present study was to explore the potential associations between the 5-HTR2A and IL-6 single-nucleotide polymorphisms (SNPs) and OSAHS. In total there were 130 cases and 136 controls collected for genotyping of 5-HTR2A (rs6311) and IL-6 (rs1800796) SNPs. The association of these SNPs with OSAHS risk were evaluated by computing the odds ratio (OR) and 95% confidence interval (CI) from multivariate unconditional logistic regression analyses with adjustment for gender and age. The results indicated that the genotype and allele frequencies in these two loci (rs6311 and rs1800796) were not significantly different between the cases and controls. However, carrying the 'C' allele of rs6311 has a protective effect against OSAHS via the gender-specific comparison (P=0.0409; OR, 1.744; 95% CI, 1.021-2.978). The 'G' allele and 'CG' genotype distribution of rs1800796, and 'C' allele and 'CT' genotype distribution of rs6311 have significant differences between the mild and moderate group (P<0.05). Similarly, the genotype distribution of rs6311 has differences between mild and severe cases (P=0.0026). The current research demonstrated that variants of rs6311 have an association with OSAHS in males. Additionally, polymorphisms of rs6311 and rs1800796 have relevance to the severity of OSAHS.
| S-EPMC4734233 | biostudies-literature
Project description:ObjectiveTo assess sleepiness, TNF-? plasma levels, and genomic variance in the TNF-? gene in children with obstructive sleep apnea (OSA).Study designChildren being evaluated for OSA (n = 60) and matched control children (n = 80) were assessed with a modified Epworth Sleepiness Scale questionnaire and underwent a blood draw the morning after nocturnal polysomnography. TNF-? plasma concentrations were assayed using ELISA, and genomic DNA was extracted. Genotyping and allelic frequencies were determined for 4 TNF-? single nucleotide polymorphisms using real-time polymerase chain reaction genotyping assays.ResultsMorning TNF-? levels and Epworth Sleepiness Scale scores were increased in the presence of OSA, but substantial variability was present. Although TNF-? plasma concentrations were globally increased in OSA, most of the variance was attributable to the presence or absence of TNF-? -308G gene polymorphism.ConclusionsTNF-? levels are increased in a subset of children with OSA, particularly among those harboring the TNF-? -308G single nucleotide polymorphism. Among the latter, significant increases in excessive daytime sleepiness symptoms are also present. The relatively high variability of excessive daytime sleepiness in pediatric OSA may be related to underlying TNF-? gene polymorphisms, particularly -308G.
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Project description:Illumina MiSeq next generation sequencing chip was used to identify differentially expressed miRs by comparing peripheral blood mononuclear cell samples between OSA patients and healthy non-snorers.
2021-12-01 | GSE174245 | GEO
Project description:IntroductionObstructive sleep apnea (OSA) subjects show impaired autonomic, affective, executive, sensorimotor, and cognitive functions. Brain injury in OSA subjects appears in multiple sites regulating these functions, but the integrity of functional networks within the regulatory sites remains unclear. Our aim was to examine the functional interactions and the complex network organization of these interactions across the whole brain in OSA, using regional functional connectivity (FC) and brain network topological properties.MethodsWe collected resting-state functional magnetic resonance imaging (MRI) data, using a 3.0-Tesla MRI scanner, from 69 newly diagnosed, treatment-naïve, moderate-to-severe OSA (age, 48.3 ± 9.2 years; body mass index, 31 ± 6.2 kg/m(2); apnea-hypopnea index (AHI), 35.6 ± 23.3 events/h) and 82 control subjects (47.6 ± 9.1 years; body mass index, 25.1 ± 3.5 kg/m(2)). Data were analyzed to examine FC in OSA over controls as interregional correlations and brain network topological properties.ResultsObstructive sleep apnea subjects showed significantly altered FC in the cerebellar, frontal, parietal, temporal, occipital, limbic, and basal ganglia regions (FDR, P < 0.05). Entire functional brain networks in OSA subjects showed significantly less efficient integration, and their regional topological properties of functional integration and specialization characteristics also showed declined trends in areas showing altered FC, an outcome which would interfere with brain network organization (P < 0.05; 10,000 permutations). Brain sites with abnormal topological properties in OSA showed significant relationships with AHI scores.ConclusionsOur findings suggest that the dysfunction extends to resting conditions, and the altered FC and impaired network organization may underlie the impaired responses in autonomic, cognitive, and sensorimotor functions. The outcomes likely result from the prominent structural changes in both axons and nuclear structures, which occur in the condition.
| S-EPMC4831421 | biostudies-literature
Project description:Study objectivesThe aim of the study was to investigate the effect of ambient temperature on sleep, sleep apnea, and morning alertness in patients with obstructive sleep apnea.DesignRandomized controlled trial.SettingIn-hospital investigations.ParticipantsForty patients with obstructive sleep apnea naïve to treatment, with an apnea-hypopnea index of 10-30.InterventionsThree different nights in room temperatures of 16°C, 20°C, and 24°C.MeasurementsOvernight polysomnography and Karolinska Sleepiness Scale.ResultsThe obstructive apnea-hypopnea index was 30 ± 17 at 16°C room temperature, 28 ± 17 at 20°C, and 24 ± 18 at 24°C. The obstructive apnea-hypopnea index was higher at 16°C room temperature versus 24°C (P = 0.001) and at 20°C room temperature versus 24°C (P = 0.033). Total sleep time was a mean of 30 min longer (P = 0.009), mean sleep efficiency was higher (77 ± 11% versus 71 ± 13% respectively, P = 0.012), and the patients were significantly more alert according to the Karolinska Sleepiness Scale (P < 0.028) in the morning at 16°C room temperature versus 24°C. The amount of sleep in different sleep stages was not affected by room temperature.ConclusionsUntreated patients with obstructive sleep apnea sleep longer, have better sleep efficiency, and are more alert in the morning after a night's sleep at 16°C room temperature compared with 24°C, but obstructive sleep apnea is more severe at 16°C and 20°C compared with 24°C.Clinical trial informationThis study is registered in ClinicalTrials.gov number NCT00544752.
| S-EPMC3296793 | biostudies-literature
Project description:IntroductionEnhanced characterization of sleep architecture, compared with routine polysomnographic metrics such as stage percentages and sleep efficiency, may improve the predictive phenotyping of fragmented sleep. One approach involves using stage transition analysis to characterize sleep continuity.Methods and principal findingsWe analyzed hypnograms from Sleep Heart Health Study (SHHS) participants using the following stage designations: wake after sleep onset (WASO), non-rapid eye movement (NREM) sleep, and REM sleep. We show that individual patient hypnograms contain insufficient number of bouts to adequately describe the transition kinetics, necessitating pooling of data. We compared a control group of individuals free of medications, obstructive sleep apnea (OSA), medical co-morbidities, or sleepiness (n = 374) with mild (n = 496) or severe OSA (n = 338). WASO, REM sleep, and NREM sleep bout durations exhibited multi-exponential temporal dynamics. The presence of OSA accelerated the "decay" rate of NREM and REM sleep bouts, resulting in instability manifesting as shorter bouts and increased number of stage transitions. For WASO bouts, previously attributed to a power law process, a multi-exponential decay described the data well. Simulations demonstrated that a multi-exponential process can mimic a power law distribution.Conclusion and significanceOSA alters sleep architecture dynamics by decreasing the temporal stability of NREM and REM sleep bouts. Multi-exponential fitting is superior to routine mono-exponential fitting, and may thus provide improved predictive metrics of sleep continuity. However, because a single night of sleep contains insufficient transitions to characterize these dynamics, extended monitoring of sleep, probably at home, would be necessary for individualized clinical application.
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Project description:Obstructive sleep apnea (OSA) has been linked to dysregulated metabolic states and treatment of sleep apnea may improve these conditions. Subcutaneous adipose tissue is a readily samplable fat depot that plays an important role in regulating metabolism. However, neither the pathophysiologic consequences of OSA nor the effects of continuous positive airway pressure (CPAP) in altering this compartment’s molecular pathways are understood. This study aimed to systematically identify subcutaneous adipose tissue transcriptional programs modulated in OSA and in response to its effective treatment with CPAP. Two subject groups were investigated: Study Group 1 was comprised of 10 OSA and 8 controls; Study Group 2 included 24 individuals with OSA studied at baseline and following CPAP. For each subject, genome-wide gene expression measurement of subcutaneous fat was performed. Differentially activated pathways elicited by OSA (Group 1) and in response to its treatment (Group 2) were determined using network and Gene Set Enrichment Analysis (GSEA). In Group 2, treatment of OSA with CPAP improved apnea hypopnea index, daytime sleepiness, and blood pressure, but not anthropometric measures. In Group 1, GSEA revealed many up-regulated gene sets in OSA subjects, most of which were involved in immuno-inflammatory (e.g., interferon-γ signaling), transcription, and metabolic processes such as adipogenesis. Unexpectedly, CPAP therapy in Group 2 subjects was also associated with up-regulation of several immune pathways as well as cholesterol biosynthesis. Collectively, our findings demonstrate that OSA alters distinct inflammatory and metabolic programs in subcutaneous fat, but these transcriptional signatures are not reversed with short-term effective therapy.
2019-12-21 | GSE135917 | GEO
Project description:ObjectiveObstructive sleep apnea (OSA) is a sleep-related breathing disorder with high prevalence and is associated with cognitive impairment. Previous neuroimaging studies have reported abnormal brain functional connectivity (FC) in patients with OSA that might contribute to their neurocognitive impairments. However, it is unclear whether patients with OSA have a characteristic pattern of FC changes that can serve as a neuroimaging biomarker for identifying OSA.MethodsA total of 21 patients with OSA and 21 healthy controls (HCs) were included in this study and scanned using resting-state functional magnetic resonance imaging (fMRI). The automated anatomical labeling (AAL) atlas was used to divide the cerebrum into 90 regions, and FC between each pair of regions was calculated. Univariate analyses were then performed to detect abnormal FCs in patients with OSA compared with controls, and multivariate pattern analyses (MVPAs) were applied to classify between patients with OSA and controls.ResultsThe univariate comparisons did not detect any significantly altered FC. However, the MVPA showed a successful classification between patients with OSA and controls with an accuracy of 83.33% (p = 0.0001). Furthermore, the selected FCs were associated with nearly all brain regions and widely distributed in the whole brain, both within and between, many resting-state functional networks. Among these selected FCs, 3 were significantly correlated with the apnea-hypopnea index (AHI) and 2 were significantly correlated with the percentage of time with the saturation of oxygen (SaO2) below 90% of the total sleep time (%TST < 90%).ConclusionThere existed widespread abnormal FCs in the whole brain in patients with OSA. This aberrant FC pattern has the potential to serve as a neurological biomarker of OSA, highlighting its importance for understanding the complex neural mechanism underlying OSA and its cognitive impairment.
| S-EPMC9377518 | biostudies-literature