Multiple Allergic Rhinitis Single Nucleotide Polymorphism Variants are Associated with Sleep-Breathing Parameters in Men with Obstructive Sleep Apnea: A Large-Scale Study.

Background: Sleep-disordered breathing is more prevalent in individuals with allergic rhinitis (AR) than in those without AR. In addition to increased risk for sleep-disordered breathing, AR is associated with greater severity of obstructive sleep apnea (OSA) symptoms. The aim of this research study was to evaluate the association of multiple single nucleotide polymorphism (SNP) variations in AR with sleep- and breathing-related parameters in men with OSA. Methods: Men who had complained of snoring were consecutively enrolled in the Shanghai Sleep Health Study of Shanghai Sixth People's Hospital from 2007 to 2018. After rigorous screening, 5322 men were included in the analysis. Anthropometric, fasting biochemical, and polysomnographic parameters, along with 27 AR-associated SNPs were analyzed. The associations between AR-related genetic polymorphisms and OSA were determined via linear, binary, and multinomial logistic regression analyses. Results: Rs12509403 had significantly positive associations with most sleep-breathing parameters. While the risk for OSA was increased by rs12509403, it was decreased by rs7717955 [odds ratio (OR) = 1.341, 95% confidence interval [CI] = 1.039-1.732, P = 0.024; OR = 0.829, 95% CI = 0.715-0.961, P = 0.013, respectively]. A graded increase in the risk of being in the highest quartile (Q4) vs the reference category (Q1) for sleep breathing indicators, especially REM-AHI and NREM-AHI, was identified by rs12509403 (OR = 1.496, 95% CI = 1.175-1.904, P = 0.001; OR = 1.471, 95% CI = 1.151-1.879, P < 0.001, respectively). Conclusion: The association of multiple AR SNPs with OSA-related hypoxia and sleep indices provides a genetic explanation for the higher AR susceptibility of OSA patients. Understanding the AR-related genetic underpinnings of OSA may lead to more personalized treatment approaches.

Melatonin mediates intestinal barrier dysfunction and systemic inflammation in moderate-severe OSA patients.

BACKGROUND: Intestinal barrier dysfunction and systemic inflammation are common in obstructive sleep apnoea (OSA). We aimed to investigate the role of melatonin, an anti-inflammatory mediator, in mediating the relationships between OSA, intestinal barrier dysfunction and systemic inflammation. METHODS: Two hundred and thirty-five male participants who complained with sleep problems and underwent whole night polysomnography at our sleep centre between 2017 and 2018 were enrolled. Polysomnographic data, anthropometric measurements and biochemical indicators were collected. Serum melatonin, intestinal barrier function biomarker zonula occludens-1 (ZO-1) and inflammatory biomarkers C-reactive protein (CRP) with lipopolysaccharide (LPS) were detected. Spearman's correlation analysis assessed the correlations between sleep parameters, melatonin and biomarkers (ZO-1, LPS and CRP). Mediation analysis explored the effect of OSA on intestinal barrier dysfunction and systemic inflammation in moderate-severe OSA patients. RESULTS: As OSA severity increased, serum melatonin decreased, whereas ZO-1, LPS and CRP increased. Spearman's correlation analysis showed that serum melatonin was significantly negatively correlated with ZO-1 (r = -0.19, p < .05) and LPS (r = -0.20, p < .05) in the moderate-OSA group; serum melatonin was significantly negatively correlated with ZO-1 (r = -0.46, p < .01), LPS (r = -0.35, p < .01) and CPR (r = -0.30, p < .05) in the severe-OSA group. Mediation analyses showed melatonin explain 36.12% and 35.38% of the effect of apnoea-hypopnea index (AHI) on ZO-1 and LPS in moderate to severe OSA patients. CONCLUSIONS: Our study revealed that melatonin may be involved in mediating intestinal barrier dysfunction and systemic inflammation in moderate-to-severe OSA patients.

Genetic variations of low-density lipoprotein cholesterol on metabolic disorders in obstructive sleep apnea.

BACKGROUND: The study aimed to explore the relationship between low-density lipoprotein cholesterol (LDL-C) genetic variants and obstructive sleep apnea (OSA) and its complications, including cardiovascular diseases (CVD), insulin resistance (IR), and metabolic syndrome (MS). METHOD: 4329 individuals with suspected OSA who underwent a comprehensive assessment of anthropometric, biochemical, and polysomnography (PSG) data, along with 30 LDL-C single nucleotide polymorphisms (SNPs) were enrolled. The 10-year Framingham CVD risk score (FRS), IR and MS were evaluated for each subject. Linear regression and logistic regression were utilized to examine the correlations among these variables. RESULTS: After the Benjamini-Hochberg correction, linear regression results indicated positive correlations between variants rs3741297 and rs629301 with FRS (ß = 0.031, PBH=0.002; ß = 0.026, PBH=0.015). Logistic regression revealed that rs3741297 increased MS risk among total subjects [OR = 1.67 (95% CI:1.369-2.038), PBH=1.32 × 10- 5] and increased IR risk in females [OR = 3.475 (95% CI:1.653-7.307), PBH=0.03]. In males, rs2642438 decreased MS risk [OR = 0.81 (95% CI:0.703-0.933), PBH=0.045]. CONCLUSIONS: The rs3741297 variant correlated with susceptibility to CVD, IR, and MS in the OSA population. OSA, CVD, IR and MS share a potentially common genetic background, which may promote precision medicine. CINICAL TRIAL REGISTRATION: The study protocol was registered with the Chinese Clinical Trial Registry (ChiCTR1900025714).

T266M variants of ANGPTL4 improve lipid metabolism by modifying their binding affinity to acetyl-CoA carboxylase in obstructive sleep apnea.

BACKGROUND: Angiopoietin-like protein 4 (ANGPTL4) is recognized as a crucial regulator in lipid metabolism. Acetyl-CoA carboxylases (ACACAs) play a role in the ß-oxidation of fatty acids. Yet, the functions of ANGPTL4 and ACACA in dyslipidemia of obstructive sleep apnea (OSA) remain unclear. METHODS: This study included 125 male OSA subjects from the Shanghai Sleep Health Study (SSHS) who were matched for age, body mass index (BMI), and lipid profile. Serum ANGPTL4 levels were measured via ELISA. The ANGPTL4 T266M variants of 4455 subjects along with their anthropometric, fasting biochemical, and standard polysomnographic parameters were collected. Linear regression was used to analyze the associations between quantitative traits and ANGPTL4 T266M. Molecular docking and molecular dynamic simulation were employed to compare the effects of the wild-type ANGPTL4 and its T266M mutation on ACACA. RESULTS: Serum ANGPTL4 levels significantly decreased with increasing OSA severity (non-OSA: 59.6 ± 17.4 ng/mL, mild OSA: 50.0 ± 17.5 ng/mL, moderate OSA: 46.3 ± 15.5 ng/mL, severe OSA: 19.9 ± 14.3 ng/mL, respectively, p = 6.02 × 10-16). No associations were found between T266M and clinical characteristics. Molecular docking indicated that mutant ANGTPL4 T266M had stronger binding affinity for the ACACA protein, compared with wild-type ANGPTL4. In terms of protein secondary structure, mutant ANGTPL4 T266M demonstrated greater stability than wild-type ANGPTL4. CONCLUSIONS: Serum ANGTPL4 levels were significantly decreased in OSA patients, particularly among individuals with severe OSA. Although functional ANGTPL4 T266M variants were not associated with lipid levels in OSA, ANGTPL4 T266M could enhance binding affinity for the ACACA protein, potentially regulating lipid metabolism.