Association between genetic variants in metabolic syndrome-related genes and risk of obstructive sleep apnea among a Chinese population

Abstract Background Despite the strong epidemiological association between Metabolic syndrome (MetS) and obstructive sleep apnea (OSA), the causal mechanism between the two remains not fully elucidated. We conducted a case-control study to evaluate the genetic association of twelve metabolic syndrome-related genes with OSA in Chinese subjects. Methods Targeted capture sequencing for twelve metabolic syndrome-related genes (EDN1, APOE, LEP, LEPR, IRS1, UCP1, ADIPOQ, PEMT, PPARG, SLC2A4, FABP2 and ADRA2A) were performed in 100 subjects including 50 patients with severe OSA and 50 non-OSA individuals. Possible associations between genetic variants and the risk of OSA were determined by logistic regression analyses. Results From the multiple genes studied, only the rs12486170 variant in PPARG gene was associated with OSA risk after adjusting for potential confounding factors. The PPARG rs12486170 AG/GG genotype was found to decrease the risk for OSA [dominant model: adjusted odds ratio (AOR) = 0.211, 95% confidence interval (CI) = 0.055-0.800, P = 0.022] compared with AA genotype. Moreover, subjects with the rs12486170 AG/GG genotype had a significantly lower apnea-hypopnea index (AHI) (median: 2.50 vs. 50.90 events/h, P = 0.019) and higher lowest oxygen saturation (LSaO2) (median: 87% vs. 75%, P = 0.040) compared with those with the AA genotype. Conclusions We identified a novel variant of PPARG in subjects with OSA, and specifically found an association between rs12486170 polymorphisms and OSA risk in a Chinese population.

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Abstract 16780: Effects of Ethnicity on the Prevalence of Obstructive Sleep Apnea in Patients With Acute Coronary Syndrome: A Pooled Analysis of the ISAACC Trial and Sleep and Stent Study

Circulation ◽

10.1161/circ.132.suppl_3.16780 ◽

2015 ◽

Vol 132 (suppl_3) ◽

Author(s):

Chieh Yang Koo ◽

Keyword(s):

Obstructive Sleep Apnea ◽

Acute Coronary Syndrome ◽

Sleep Apnea ◽

Chinese Population ◽

Pooled Analysis ◽

Forest Plot ◽

Apnea Hypopnea Index ◽

Sleep Study ◽

Coronary Syndrome ◽

Obstructive Sleep

Objective: Obstructive sleep apnea (OSA) is an increasing yet under-recognized risk factor for acute coronary syndrome (ACS). We sought to determine the effects of ethnicity on the prevalence of OSA in patients presenting with ACS who participated in an overnight sleep study. Methods: A pooled analysis using patient-level data from the ISAACC Trial and Sleep and Stent Study was performed. In both of these studies, patients presenting with ACS were recruited to undergo an overnight sleep study. OSA was defined as an apnea-hypopnea index (AHI) of ≥15. A bivariate analysis of the factors affecting AHI and an age-adjusted analysis of the effect of BMI on sleep apnea according to ethnicity were conducted. Results: A total of 1961 patients were analyzed, including Spanish (53.6%, n=1050), Chinese (25.5%, n=500), Indian (12.0%, n=235), Malay (6.1%, n=119), Brazilian (1.7%, n=34) and Burmese (1.2%, n=23) populations. Significant differences in body mass index (BMI) were found among the various ethnic groups, averaging from 25.3 kg/m2 for Indians and 25.4 kg/m2 for Chinese to 28.6 kg/m2 for Spaniards. The prevalence of OSA was highest in the Spanish (63.1%), followed by the Chinese (50.2%), Malay (47.9%), Burmese (43.5%), Brazilian (41.2%), and Indian patients. Figure 1 shows the forest plot of the prevalence of OSA among the various ethnicities. A significant interaction between BMI and ethnicity to predict OSA was observed. The estimated odds ratio of BMI on OSA was highest in the Chinese population (1.17; 95% confidence interval: 1.10-1.24), but was not significant in the Spanish, Burmese or Brazilian populations. The area under the curve for the Asian patients (ranging from 0.6365 to 0.6692) was higher than that for the Spanish patients (0.5161). Conclusion: There was significant ethnic variation in the prevalence of OSA in patients with ACS, and the magnitude of the effect of BMI on OSA was greater in the Chinese population than in the Spanish patients.

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Time delay of baroreflex control and oscillatory pattern of sympathetic activity in patients with metabolic syndrome and obstructive sleep apnea

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.00848.2012 ◽

2013 ◽

Vol 304 (7) ◽

pp. H1038-H1044 ◽

Cited By ~ 18

Author(s):

Edgar Toschi-Dias ◽

Ivani C. Trombetta ◽

Valdo J. Dias da Silva ◽

Cristiane Maki-Nunes ◽

Felipe X. Cepeda ◽

...

Keyword(s):

Metabolic Syndrome ◽

Obstructive Sleep Apnea ◽

Sleep Apnea ◽

Time Delay ◽

Sympathetic Activity ◽

Apnea Hypopnea Index ◽

Baroreflex Control ◽

Oscillatory Pattern ◽

Obstructive Sleep ◽

The Impact

The incidence and strength of muscle sympathetic nerve activity (MSNA) depend on the magnitude (gain) and latency (time delay) of the arterial baroreflex control (ABR). However, the impact of metabolic syndrome (MetS) and obstructive sleep apnea (OSA) on oscillatory pattern of MSNA and time delay of the ABR of sympathetic activity is unknown. We tested the hypothesis that MetS and OSA would impair the oscillatory pattern of MSNA and the time delay of the ABR of sympathetic activity. Forty-three patients with MetS were allocated into two groups according to the presence of OSA (MetS + OSA, n = 21; and MetS − OSA, n = 22). Twelve aged-paired healthy controls (C) were also studied. OSA (apnea-hypopnea index > 15 events/h) was diagnosed by polysomnography. We recorded MSNA (microneurography), blood pressure (beat-to-beat basis), and heart rate (EKG). Oscillatory pattern of MSNA was evaluated by autoregressive spectral analysis and the ABR of MSNA (ABRMSNA, sensitivity and time delay) by bivariate autoregressive analysis. Patients with MetS + OSA had decreased oscillatory pattern of MSNA compared with MetS − OSA ( P < 0.01) and C ( P < 0.001). The sensitivity of the ABRMSNA was lower and the time delay was greater in MetS + OSA compared with MetS − OSA ( P < 0.001 and P < 0.01, respectively) and C ( P < 0.001 and P < 0.001, respectively). Patients with MetS − OSA showed decreased oscillatory pattern of MSNA compared with C ( P < 0.01). The sensitivity of the ABRMSNA was lower in MetS − OSA than in C group ( P < 0.001). In conclusion, MetS decreases the oscillatory pattern of MSNA and the magnitude of the ABRMSNA. OSA exacerbates these autonomic dysfunctions and further increases the time delay of the baroreflex response of MSNA.

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Association of Metabolic Syndrome With Prevalence of Obstructive Sleep Apnea and Remission After Sleeve Gastrectomy

Frontiers in Physiology ◽

10.3389/fphys.2021.650260 ◽

2021 ◽

Vol 12 ◽

Author(s):

Yufei Chen ◽

Lijia Chen ◽

Lingxia Ye ◽

Jiabin Jin ◽

Yingkai Sun ◽

...

Keyword(s):

Metabolic Syndrome ◽

Obstructive Sleep Apnea ◽

Sleeve Gastrectomy ◽

Sleep Apnea ◽

Laparoscopic Sleeve Gastrectomy ◽

Apnea Hypopnea Index ◽

Obese Patients ◽

Metabolic States ◽

Obstructive Sleep ◽

Metabolically Healthy

Obesity is an important risk factor for metabolic syndrome and obstructive sleep apnea (OSA). Bariatric surgery has been shown to effectively reduce weight and obesity-related comorbidities. However, the prevalence and severity of OSA in obese patients with different baseline metabolic states and the improvements of OSA after bariatric surgery remain unknown. The main aims of this study were to ascertain the prevalence of OSA in young Chinese obese patients with different metabolic states and to evaluate their respective OSA remission after laparoscopic sleeve gastrectomy. We first performed a cross-sectional study involving 123 metabolically healthy obese patients and 200 metabolically unhealthy obese patients (who had the same age and BMI ranges) to estimate the prevalence of OSA at baseline. Then we performed a retrospective study, which was registered at ClinicalTrials.gov (ref. NCT02653430) of 67 patients who underwent laparoscopic sleeve gastrectomy to evaluate the remission of OSA. Metabolically healthy and unhealthy obese patients had similar apnea-hypopnea index levels (16.6 ± 22.0 vs. 16.7 ± 18.7 events/h, P = 0.512) and prevalence of OSA (66.7% vs. 69.0%, P = 0.662). Male sex, age, waist circumference and lower liver-to-spleen ratio were independent risk factors for OSA. After laparoscopic sleeve gastrectomy, no difference was found in the decrease in body mass index (BMI) change (10.8 ± 4.8 vs. 10.8 ± 3.0 kg/m2, P = 0.996) or the decrease in the apnea-hypopnea index (18.9 ± 24.6 vs. 17.0 ± 24.0 events/h, P = 0.800). The remission of moderate-to-severe OSA was observed in the MHO (36.3%; 54.5–18.2%, P = 0.125) and MUO (32.2%; 66.1–33.9%, P = 0.001) patients. These results suggest that, in patients with obesity, metabolic syndrome does not add extra risk for the prevalence or severity of OSA. Both metabolically healthy and unhealthy obese patients could benefit equally from laparoscopic sleeve gastrectomy in terms of weight loss and obstructive sleep apnea remission.

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Improvement in Obstructive Sleep Apnea (OSA) in Super Morbidly Obese Patients After Bariatric Surgery

Journal of the Medical Association of Thailand ◽

10.35755/jmedassocthai.2020.08.10650 ◽

2020 ◽

Vol 103 (8) ◽

pp. 725-728

Keyword(s):

Bariatric Surgery ◽

Obstructive Sleep Apnea ◽

Sleep Apnea ◽

Lifestyle Modification ◽

Apnea Hypopnea Index ◽

Morbidly Obese ◽

Obese Patients ◽

Obstructive Sleep ◽

Objective Evidence

Background: Lifestyle modification is the mainstay therapy for obese patients with obstructive sleep apnea (OSA). However, most of these patients are unable to lose the necessary weight, and bariatric surgery (BS) has been proven to be an effective modality in selected cases. Objective: To provide objective evidence that BS can improve OSA severity. Materials and Methods: A prospective study was conducted in super morbidly obese patients (body mass index [BMI] greater than 40 kg/m² or BMI greater than 35 kg/m² with uncontrolled comorbidities) scheduled for BS. Polysomnography (PSG) was performed for preoperative assessment and OSA was treated accordingly. After successful surgery, patients were invited to perform follow-up PSG at 3, 6, and 12 months. Results: Twenty-four patients with a mean age of 35.0±14.0 years were enrolled. After a mean follow-up period of 7.8±3.4 months, the mean BMI, Epworth sleepiness scale (ESS), and apnea-hypopnea index (AHI) significantly decreased from 51.6±8.7 to 38.2±6.8 kg/m² (p<0.001), from 8.7±5.9 to 4.7±3.5 (p=0.003), and from 87.6±38.9 to 28.5±21.5 events/hour (p<0.001), respectively. Conclusion: BS was shown to dramatically improve clinical and sleep parameters in super morbidly obese patients. Keywords: Morbid obesity, Bariatric surgery, Obstructive sleep apnea (OSA)

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Aerodynamics Analysis of the Impact of Nasal Surgery on Patients with Obstructive Sleep Apnea and Nasal Obstruction

ORL ◽

10.1159/000516243 ◽

2021 ◽

pp. 1-8

Author(s):

Lifeng Li ◽

Demin Han ◽

Hongrui Zang ◽

Nyall R. London

Keyword(s):

Obstructive Sleep Apnea ◽

Sleep Apnea ◽

Nasal Obstruction ◽

Upper Airway ◽

Apnea Hypopnea Index ◽

Nasal Surgery ◽

Subjective Sleep Quality ◽

Obstructive Sleep ◽

Significant Difference ◽

The Impact

Objective: The purpose of this study was to evaluate the effects of nasal surgery on airflow characteristics in patients with obstructive sleep apnea (OSA) by comparing the alterations of airflow characteristics within the nasal and palatopharyngeal cavities. Methods: Thirty patients with OSA and nasal obstruction who underwent nasal surgery were enrolled. A pre- and postoperative 3-dimensional model was constructed, and alterations of airflow characteristics were assessed using the method of computational fluid dynamics. The other subjective and objective clinical indices were also assessed. Results: By comparison with the preoperative value, all postoperative subjective symptoms statistically improved (p < 0.05), while the Apnea-Hypopnea Index (AHI) changed little (p = 0.492); the postoperative airflow velocity and pressure in both nasal and palatopharyngeal cavities, nasal and palatopharyngeal pressure differences, and total upper airway resistance statistically decreased (all p < 0.01). A significant difference was derived for correlation between the alteration of simulation metrics with subjective improvements (p < 0.05), except with the AHI (p > 0.05). Conclusion: Nasal surgery can decrease the total resistance of the upper airway and increase the nasal airflow volume and subjective sleep quality in patients with OSA and nasal obstruction. The altered airflow characteristics might contribute to the postoperative reduction of pharyngeal collapse in a subset of OSA patients.

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Klotho genetic variants mediate the association between obstructive sleep apnea and short telomere length

Sleep Medicine ◽

10.1016/j.sleep.2021.01.015 ◽

2021 ◽

Author(s):

Priscila Farias Tempaku ◽

Vânia D’Almeida ◽

Sylvia Maria Affonso da Silva ◽

Monica Levy Andersen ◽

Sintia Iole Belangero ◽

...

Keyword(s):

Obstructive Sleep Apnea ◽

Sleep Apnea ◽

Telomere Length ◽

Genetic Variants ◽

Short Telomere ◽

Obstructive Sleep

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Understanding the role of oxidative stress in the incidence of metabolic syndrome and obstructive sleep apnea

BMC Endocrine Disorders ◽

10.1186/s12902-021-00735-4 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Behnam Kargar ◽

Zahra Zamanian ◽

Majid Bagheri Hosseinabadi ◽

Vahid Gharibi ◽

Mohammad Sanyar Moradi ◽

...

Keyword(s):

Oxidative Stress ◽

Metabolic Syndrome ◽

Obstructive Sleep Apnea ◽

Logistic Regression ◽

Sleep Apnea ◽

International Diabetes Federation ◽

Binary Logistic Regression ◽

Stress Index ◽

Obstructive Sleep

Abstract Background Understanding the causes and risk factors of metabolic syndrome is important for promoting population health. Oxidative stress has been associated with metabolic syndrome, and also obstructive sleep apnea. These are two diseases which have common prognostic characteristics for heart disease. The aim of this study was to examine the role of oxidative stress in the concurrent presence of metabolic syndrome and obstructive sleep apnea in a working population. Methods Participants were 163 artisan bakers in Shahroud, Iran, routinely exposed to significant heat stress and other oxidative stress indicators on a daily basis as part of their work. Using a cross-sectional design, data relevant to determining metabolic syndrome status according to International Diabetes Federation criteria, and the presence of obstructive sleep apnea according to the STOP-Bang score, was collected. Analyses included hierarchical binary logistic regression to yield predictors of the two diseases. Results Hierarchical binary logistic regression showed that oxidative stress – alongside obesity, no regular exercise, and smoking – was an independent predictor of metabolic syndrome, but not obstructive sleep apnea. Participants who were obese were 28 times more likely to have metabolic syndrome (OR 28.59, 95% CI 4.91–63.02) and 44 times more likely to have obstructive sleep apnea (OR 44.48, 95% CI 4.91–403.28). Participants meeting metabolic syndrome criteria had significantly higher levels of malondialdehyde (p < 0.05) than those who did not. No difference in oxidative stress index levels were found according to obstructive sleep apnea status. Conclusions Our findings suggest that oxidative stress contributes to the onset of metabolic syndrome, and that obstructive sleep apnea is involved in oxidative stress. Whilst obesity, exercise, and smoking remain important targets for reducing the incidence of metabolic syndrome and obstructive sleep apnea, policies to control risks of prolonged exposure to oxidative stress are also relevant in occupations where such environmental conditions exist.

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High Plasma Cystine Levels Are Associated with Blood Pressure and Reversed by CPAP in Patients with Obstructive Sleep Apnea

Journal of Clinical Medicine ◽

10.3390/jcm10071387 ◽

2021 ◽

Vol 10 (7) ◽

pp. 1387

Author(s):

Raphael Boneberg ◽

Anita Pardun ◽

Lena Hannemann ◽

Olaf Hildebrandt ◽

Ulrich Koehler ◽

...

Keyword(s):

Blood Pressure ◽

Obstructive Sleep Apnea ◽

Sleep Apnea ◽

Mononuclear Cells ◽

Vascular Risk Factor ◽

High Plasma ◽

Apnea Hypopnea Index ◽

Hypoxic Stress ◽

Peripheral Blood Mononuclear ◽

Obstructive Sleep

Obstructive sleep apnea (OSA) independent of obesity (OBS) imposes severe cardiovascular risk. To what extent plasma cystine concentration (CySS), a novel pro-oxidative vascular risk factor, is increased in OSA with or without OBS is presently unknown. We therefore studied CySS together with the redox state and precursor amino acids of glutathione (GSH) in peripheral blood mononuclear cells (PBMC) in untreated male patients with OSA (apnea-hypopnea-index (AHI) > 15 h−1, n = 28) compared to healthy male controls (n = 25) stratifying for BMI ≥ or < 30 kg m−2. Fifteen OSA patients were reassessed after 3–5-months CPAP. CySS correlated with cumulative time at an O2-saturation <90% (Tu90%) (r = 0.34, p < 0.05) beside BMI (r = 0.58, p < 0.001) and was higher in subjects with “hypoxic stress” (59.4 ± 2.0 vs. 50.1 ± 2.7 µM, p < 0.01) defined as Tu90% ≥ 15.2 min (corresponding to AHI ≥ 15 h−1). Moreover, CySS significantly correlated with systolic (r = 0.32, p < 0.05) and diastolic (r = 0.31, p < 0.05) blood pressure. CPAP significantly lowered CySS along with blood pressure at unchanged BMI. Unexpectedly, GSH antioxidant capacity in PBMC was increased with OSA and reversed with CPAP. Plasma CySS levels are increased with OSA-related hypoxic stress and associated with higher blood pressure. CPAP decreases both CySS and blood pressure. The role of CySS in OSA-related vascular endpoints and their prevention by CPAP warrants further studies.

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Altered K-complex morphology during sustained inspiratory airflow limitation is associated with next-day lapses in vigilance in obstructive sleep apnea

SLEEP ◽

10.1093/sleep/zsab010 ◽

2021 ◽

Author(s):

Ankit Parekh ◽

Korey Kam ◽

Anna E Mullins ◽

Bresne Castillo ◽

Asem Berkalieva ◽

...

Keyword(s):

Obstructive Sleep Apnea ◽

Sleep Apnea ◽

Spectral Characteristics ◽

Sleep Time ◽

Airflow Limitation ◽

Apnea Hypopnea Index ◽

Complex Morphology ◽

Obstructive Sleep ◽

Inspiratory Airflow Limitation ◽

Psychomotor Vigilance

Abstract Study Objectives Determine if changes in K-complexes associated with sustained inspiratory airflow limitation (SIFL) during N2 sleep are associated with next-day vigilance and objective sleepiness. Methods Data from thirty subjects with moderate-to-severe obstructive sleep apnea who completed three in-lab polysomnograms: diagnostic, on therapeutic continuous positive airway pressure (CPAP), and on suboptimal CPAP (4 cmH2O below optimal titrated CPAP level) were analyzed. Four 20-min psychomotor vigilance tests (PVT) were performed after each PSG, every 2 h. Changes in the proportion of spontaneous K-complexes and spectral characteristics surrounding K-complexes were evaluated for K-complexes associated with both delta (∆SWAK), alpha (∆αK) frequencies. Results Suboptimal CPAP induced SIFL (14.7 (20.9) vs 2.9 (9.2); %total sleep time, p < 0.001) with a small increase in apnea–hypopnea index (AHI3A: 6.5 (7.7) vs 1.9 (2.3); p < 0.01) versus optimal CPAP. K-complex density (num./min of stage N2) was higher on suboptimal CPAP (0.97 ± 0.7 vs 0.65±0.5, #/min, mean ± SD, p < 0.01) above and beyond the effect of age, sex, AHI3A, and duration of SIFL. A decrease in ∆SWAK with suboptimal CPAP was associated with increased PVT lapses and explained 17% of additional variance in PVT lapses. Within-night during suboptimal CPAP K-complexes appeared to alternate between promoting sleep and as arousal surrogates. Electroencephalographic changes were not associated with objective sleepiness. Conclusions Sustained inspiratory airflow limitation is associated with altered K-complex morphology including the increased occurrence of K-complexes with bursts of alpha as arousal surrogates. These findings suggest that sustained inspiratory flow limitation may be associated with nonvisible sleep fragmentation and contribute to increased lapses in vigilance.

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