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Chin-chou Wang - One of the best experts on this subject based on the ideXlab platform.

  • Whole Genome DNA Methylation Analysis of Obstructive Sleep Apnea: IL1R2/ NPR2/ AR/ SP140 Methylation and Clinical Phenotype.
    Sleep, 2016
    Co-Authors: Yung-che Chen, Ting-wen Chen, Chung-jen Chen, Kuang-den Chen, Chia-wei Liou, Petrus Tang, Ting-ya Wang, Jen-chieh Chang, Chin-chou Wang
    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.

  • whole genome dna methylation analysis of obstructive sleep apnea il1r2 npr2 ar sp140 methylation and clinical phenotype
    Sleep, 2016
    Co-Authors: Yung-che Chen, Ting-wen Chen, Chung-jen Chen, Kuang-den Chen, Chia-wei Liou, Petrus Tang, Ting-ya Wang, Jen-chieh Chang, Chin-chou Wang, Hsinching Lin
    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.

Yung-che Chen - One of the best experts on this subject based on the ideXlab platform.

  • Whole Genome DNA Methylation Analysis of Obstructive Sleep Apnea: IL1R2/ NPR2/ AR/ SP140 Methylation and Clinical Phenotype.
    Sleep, 2016
    Co-Authors: Yung-che Chen, Ting-wen Chen, Chung-jen Chen, Kuang-den Chen, Chia-wei Liou, Petrus Tang, Ting-ya Wang, Jen-chieh Chang, Chin-chou Wang
    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.

  • whole genome dna methylation analysis of obstructive sleep apnea il1r2 npr2 ar sp140 methylation and clinical phenotype
    Sleep, 2016
    Co-Authors: Yung-che Chen, Ting-wen Chen, Chung-jen Chen, Kuang-den Chen, Chia-wei Liou, Petrus Tang, Ting-ya Wang, Jen-chieh Chang, Chin-chou Wang, Hsinching Lin
    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.

Yingying Wei - One of the best experts on this subject based on the ideXlab platform.

  • Detection of cell-type-specific risk-CpG Sites in epigenome-wide association studies
    Nature Communications, 2019
    Co-Authors: Xiangyu Luo, Can Yang, Yingying Wei
    Abstract:

    In epigenome-wide association studies, the measured signals for each sample are a mixture of methylation profiles from different cell types. Current approaches to the association detection claim whether a cytosine-phosphate-guanine (CpG) Site is associated with the phenotype or not at aggregate level and can suffer from low statistical power. Here, we propose a statistical method, HIgh REsolution (HIRE), which not only improves the power of association detection at aggregate level as compared to the existing methods but also enables the detection of risk-CpG Sites for individual cell types.Cellular heterogeneity is one of the major confounding factors in EWAS studies. Here the authors present a statistical method, HIgh REsolution (HIRE), which enables the detection of risk-CpG Sites for individual cell types.

  • Detection of cell-type-specific risk-CpG Sites in epigenome-wide association studies
    2018
    Co-Authors: Xiangyu Luo, Can Yang, Yingying Wei
    Abstract:

    In epigenome-wide association studies, the measured signals for each sample are a mixture of methylation profiles from different cell types. The current approaches to the association detection only claim whether a cytosine-phosphate-guanine (CpG) Site is associated with the phenotype or not, but they cannot determine the cell type in which the risk-CpG Site is affected by the phenotype. Here, we propose a solid statistical method, HIgh REsolution (HIRE), which not only substantially improves the power of association detection at the aggregated level as compared to the existing methods but also enables the detection of risk-CpG Sites for individual cell types.

Zeyi Liu - One of the best experts on this subject based on the ideXlab platform.

  • methylated 322 327 CpG Site decreases hogg1 mrna expression in non small cell lung cancer
    Oncology Reports, 2017
    Co-Authors: Yuanyuan Zeng, Jianjie Zhu, Hualong Qin, Dan Shen, Zhe Lei, Zongli Ding, Jian-an Huang, Zeyi Liu
    Abstract:

    hOGG1 plays a role in several disease pathways, including various cancers. Despite such functional importance, how hOGG1 is regulated at the transcriptional level in human non-small cell lung cancer (NSCLC) remains unknown, particularly via DNA methylation changes. We obtained NSCLC tissues and adjacent non-cancerous tissues and examined hOGG1 mRNA expression levels. NSCLC cells were treated with 5-Aza to test whether DNA methylation can influence the expression of hOGG1. The MassARRAY EpiTYPER and luciferase reporter gene assays were used to define the functional region of the hOGG1 gene (including CpG Sites). Finally, ChIP assay was utilized to verify transcription factor binding to the hOGG1 5'-UTR region. Our previous studies supported the idea that the methylation of the hOGG1 gene promoter region occurs frequently in NSCLC. Treatment with 5-Aza, a demethylating agent, led to a significant restoration of hOGG1 expression in NSCLC cell lines. Quantitative PCR and MassARRAY EpiTYPER assays demonstrated that methylation of the +322-327 CpG Site in the 5'-UTR region of hOGG1 was higher in NSCLC tissues compared with adjacent non-cancerous tissues. Notably, the methylation level of +322-327 Site (T/N) was inversely correlated with that of hOGG1 mRNA level (T/N) in 25 NSCLC tissues. ChIP assay and in silico prediction showed an association between the +322-327 CpG Site and Sp1, which has been reported to be an activator of transcription. Importantly, luciferase reporter gene and ChIP assays showed that +322-327 CpG Site methylation particularly reduced the recruitment of Sp1 to the 5'-UTR sequence in hOGG1 and reduced transcriptional activity ~50%. In summary, we have demonstrated that hOGG1 mRNA is downregulated in NSCLC tissues. Moreover, we identified that the methylated +322-327 CpG Site in the hOGG1 5'-UTR is associated with reduced expression of hOGG1 by decreasing the recruitment of Sp1 to the 5'-UTR of hOGG1.

  • Methylated +322-327 CpG Site decreases hOGG1 mRNA expression in non-small cell lung cancer
    Oncology reports, 2017
    Co-Authors: Yuanyuan Zeng, Jianjie Zhu, Hualong Qin, Dan Shen, Zhe Lei, Zongli Ding, Jian-an Huang, Zeyi Liu
    Abstract:

    hOGG1 plays a role in several disease pathways, including various cancers. Despite such functional importance, how hOGG1 is regulated at the transcriptional level in human non-small cell lung cancer (NSCLC) remains unknown, particularly via DNA methylation changes. We obtained NSCLC tissues and adjacent non-cancerous tissues and examined hOGG1 mRNA expression levels. NSCLC cells were treated with 5-Aza to test whether DNA methylation can influence the expression of hOGG1. The MassARRAY EpiTYPER and luciferase reporter gene assays were used to define the functional region of the hOGG1 gene (including CpG Sites). Finally, ChIP assay was utilized to verify transcription factor binding to the hOGG1 5'-UTR region. Our previous studies supported the idea that the methylation of the hOGG1 gene promoter region occurs frequently in NSCLC. Treatment with 5-Aza, a demethylating agent, led to a significant restoration of hOGG1 expression in NSCLC cell lines. Quantitative PCR and MassARRAY EpiTYPER assays demonstrated that methylation of the +322-327 CpG Site in the 5'-UTR region of hOGG1 was higher in NSCLC tissues compared with adjacent non-cancerous tissues. Notably, the methylation level of +322-327 Site (T/N) was inversely correlated with that of hOGG1 mRNA level (T/N) in 25 NSCLC tissues. ChIP assay and in silico prediction showed an association between the +322-327 CpG Site and Sp1, which has been reported to be an activator of transcription. Importantly, luciferase reporter gene and ChIP assays showed that +322-327 CpG Site methylation particularly reduced the recruitment of Sp1 to the 5'-UTR sequence in hOGG1 and reduced transcriptional activity ~50%. In summary, we have demonstrated that hOGG1 mRNA is downregulated in NSCLC tissues. Moreover, we identified that the methylated +322-327 CpG Site in the hOGG1 5'-UTR is associated with reduced expression of hOGG1 by decreasing the recruitment of Sp1 to the 5'-UTR of hOGG1.

Hsinching Lin - One of the best experts on this subject based on the ideXlab platform.

  • whole genome dna methylation analysis of obstructive sleep apnea il1r2 npr2 ar sp140 methylation and clinical phenotype
    Sleep, 2016
    Co-Authors: Yung-che Chen, Ting-wen Chen, Chung-jen Chen, Kuang-den Chen, Chia-wei Liou, Petrus Tang, Ting-ya Wang, Jen-chieh Chang, Chin-chou Wang, Hsinching Lin
    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.