Dataset Information

Whole Genome DNA Methylation Analysis of Obstructive Sleep Apnea: IL1R2, NPR2, AR, SP140 Methylation and Clinical Phenotype.

ABSTRACT:

Study objectives

We hypothesized that DNA methylation patterns may contribute to disease severity or the development of hypertension and excessive daytime sleepiness (EDS) in patients with obstructive sleep apnea (OSA).

Methods

Illumina's (San Diego, CA, USA) DNA methylation 27-K assay was used to identify differentially methylated loci (DML). DNA methylation levels were validated by pyrosequencing. A discovery cohort of 15 patients with OSA and 6 healthy subjects, and a validation cohort of 72 patients with sleep disordered breathing (SDB).

Results

Microarray analysis identified 636 DMLs in patients with OSA versus healthy subjects, and 327 DMLs in patients with OSA and hypertension versus those without hypertension. In the validation cohort, no significant difference in DNA methylation levels of six selected genes was found between the primary snoring subjects and OSA patients (primary outcome). However, a secondary outcome analysis showed that interleukin-1 receptor 2 (IL1R2) promoter methylation (-114 cytosine followed by guanine dinucleotide sequence [CpG] site) was decreased and IL1R2 protein levels were increased in the patients with SDB with an oxygen desaturation index > 30. Androgen receptor (AR) promoter methylation (-531 CpG site) and AR protein levels were both increased in the patients with SDB with an oxygen desaturation index > 30. Natriuretic peptide receptor 2 (NPR2) promoter methylation (-608/-618 CpG sites) were decreased, whereas levels of both NPR2 and serum C type natriuretic peptide protein were increased in the SDB patients with EDS. Speckled protein 140 (SP140) promoter methylation (-194 CpG site) was increased, and SP140 protein levels were decreased in the patients with SDB and EDS.

Conclusions

IL1R2 hypomethylation and AR hypermethylation may constitute an important determinant of disease severity, whereas NPR2 hypomethylation and SP140 hypermethylation may provide a biomarker for vulnerability to EDS in OSA.

Commentary

A commentary on this article appears in this issue on page 723.

SUBMITTER: Chen YC

PROVIDER: S-EPMC4791608 | biostudies-literature | 2016 Apr

REPOSITORIES: biostudies-literature

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Publications

Whole Genome DNA Methylation Analysis of Obstructive Sleep Apnea: IL1R2, NPR2, AR, SP140 Methylation and Clinical Phenotype.

Chen Yung-Che YC Chen Ting-Wen TW Su Mao-Chang MC Chen Chung-Jen CJ Chen Kuang-Den KD Liou Chia-Wei CW Tang Petrus P Wang Ting-Ya TY Chang Jen-Chieh JC Wang Chin-Chou CC Lin Hsin-Ching HC Chin Chien-Hung CH Huang Kuo-Tung KT Lin Meng-Chih MC Hsiao Chang-Chun CC

Sleep 20160401 4

<h4>Study objectives</h4>We hypothesized that DNA methylation patterns may contribute to disease severity or the development of hypertension and excessive daytime sleepiness (EDS) in patients with obstructive sleep apnea (OSA).<h4>Methods</h4>Illumina's (San Diego, CA, USA) DNA methylation 27-K assay was used to identify differentially methylated loci (DML). DNA methylation levels were validated by pyrosequencing. A discovery cohort of 15 patients with OSA and 6 healthy subjects, and a validatio ...[more]

PMID: 26888452

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Project description:Current evidence suggests that the pathological mechanisms underlying obstructive sleep apnea (OSA) are altered with age. However, previous studies examining individual physiological traits known to contribute to OSA pathogenesis have been assessed in isolation, primarily in healthy individuals.We assessed the four physiological traits responsible for OSA in a group of young and old patients with OSA.Sleep research laboratory.Ten young (20-40 y) and old (60 y and older) patients with OSA matched by body mass index and sex.Pharyngeal anatomy/collapsibility, loop gain (LG), upper airway muscle responsiveness/gain (UAG) and the respiratory arousal threshold were determined using multiple 2- to 3-min decreases or drops in continuous positive airway pressure (CPAP). Passive pharyngeal anatomy/collapsibility was quantified as the ventilation at CPAP = 0 cmH2O immediately after the CPAP drop. LG was defined as the ratio of the ventilatory overshoot to the preceding reduction in ventilation. UAG was taken as the ratio of the increase in ventilation to the increase in ventilatory drive across the pressure drop. Arousal threshold was estimated as the ventilatory drive that caused arousal. Veupnea was quantified as the mean ventilation prior to the pressure drop. In comparison with younger patients with OSA, older patients had a more collapsible airway (ventilation at 0 cmH2O = 3.4 ± 0.9 versus 1.5 ± 0.7 L/min; P = 0.05) but lower Veupnea (8.2 ± 0.5 versus 6.1 ± 0.4 L/min; P < 0.01) and a lower LG (5.0 ± 0.7 versus 2.9 ± 0.5; P < 0.05). The remaining traits were similar between groups.Our data suggest that airway anatomy/collapsibility plays a relatively greater pathogenic role in older adults, whereas a sensitive ventilatory control system is a more prominent trait in younger adults with obstructive sleep apnea.Edwards BA, Wellman A, Sands SA, Owens RL, Eckert DJ, White DP, Malhotra A. Obstructive sleep apnea in older adults is a distinctly different physiological phenotype.

Dataset Information

Whole Genome DNA Methylation Analysis of Obstructive Sleep Apnea: IL1R2, NPR2, AR, SP140 Methylation and Clinical Phenotype.

Study objectives

Methods

Results

Conclusions

Commentary

Publications

Whole Genome DNA Methylation Analysis of Obstructive Sleep Apnea: IL1R2, NPR2, AR, SP140 Methylation and Clinical Phenotype.

Similar Datasets

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