Cargando…
Genome-wide gene expression array identifies novel genes related to disease severity and excessive daytime sleepiness in patients with obstructive sleep apnea
We aimed to identify novel molecular associations between chronic intermittent hypoxia with re-oxygenation and adverse consequences in obstructive sleep apnea (OSA). We analyzed gene expression profiles of peripheral blood mononuclear cells from 48 patients with sleep-disordered breathing stratified...
Autores principales: | , , , , , , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2017
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5435176/ https://www.ncbi.nlm.nih.gov/pubmed/28520763 http://dx.doi.org/10.1371/journal.pone.0176575 |
_version_ | 1783237186463727616 |
---|---|
author | Chen, Yung-Che Chen, Kuang-Den Su, Mao-Chang Chin, Chien-Hung Chen, Chung-Jen Liou, Chia-Wei Chen, Ting-Wen Chang, Ya-Chun Huang, Kuo-Tung Wang, Chin-Chou Wang, Ting-Ya Chang, Jen-Chieh Lin, Yong-Yong Zheng, Yi-Xin Lin, Meng-Chih Hsiao, Chang-Chun |
author_facet | Chen, Yung-Che Chen, Kuang-Den Su, Mao-Chang Chin, Chien-Hung Chen, Chung-Jen Liou, Chia-Wei Chen, Ting-Wen Chang, Ya-Chun Huang, Kuo-Tung Wang, Chin-Chou Wang, Ting-Ya Chang, Jen-Chieh Lin, Yong-Yong Zheng, Yi-Xin Lin, Meng-Chih Hsiao, Chang-Chun |
author_sort | Chen, Yung-Che |
collection | PubMed |
description | We aimed to identify novel molecular associations between chronic intermittent hypoxia with re-oxygenation and adverse consequences in obstructive sleep apnea (OSA). We analyzed gene expression profiles of peripheral blood mononuclear cells from 48 patients with sleep-disordered breathing stratified into four groups: primary snoring (PS), moderate to severe OSA (MSO), very severe OSA (VSO), and very severe OSA patients on long-term continuous positive airway pressure treatment (VSOC). Comparisons of the microarray gene expression data identified eight genes up-regulated with OSA and down-regulated with CPAP treatment, and five genes down-regulated with OSA and up-regulated with CPAP treatment. Protein expression levels of two genes related to endothelial tight junction (AMOT P130, and PLEKHH3), and three genes related to anti-or pro-apoptosis (BIRC3, ADAR1 P150, and LGALS3) were all increased in the VSO group, while AMOT P130 was further increased, and PLEKHH3, BIRC3, and ADAR1 P150 were all decreased in the VSOC group. Subgroup analyses revealed that AMOT P130 protein expression was increased in OSA patients with excessive daytime sleepiness, BIRC3 protein expression was decreased in OSA patients with hypertension, and LGALS3 protein expression was increased in OSA patients with chronic kidney disease. In vitro short-term intermittent hypoxia with re-oxygenation experiment showed immediate over-expression of ADAR1 P150. In conclusion, we identified a novel association between AMOT/PLEKHH3/BIRC3/ADAR1/LGALS3 over-expressions and high severity index in OSA patients. AMOT and GALIG may constitute an important determinant for the development of hypersomnia and kidney injury, respectively, while BIRC3 may play a protective role in the development of hypertension. |
format | Online Article Text |
id | pubmed-5435176 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-54351762017-05-26 Genome-wide gene expression array identifies novel genes related to disease severity and excessive daytime sleepiness in patients with obstructive sleep apnea Chen, Yung-Che Chen, Kuang-Den Su, Mao-Chang Chin, Chien-Hung Chen, Chung-Jen Liou, Chia-Wei Chen, Ting-Wen Chang, Ya-Chun Huang, Kuo-Tung Wang, Chin-Chou Wang, Ting-Ya Chang, Jen-Chieh Lin, Yong-Yong Zheng, Yi-Xin Lin, Meng-Chih Hsiao, Chang-Chun PLoS One Research Article We aimed to identify novel molecular associations between chronic intermittent hypoxia with re-oxygenation and adverse consequences in obstructive sleep apnea (OSA). We analyzed gene expression profiles of peripheral blood mononuclear cells from 48 patients with sleep-disordered breathing stratified into four groups: primary snoring (PS), moderate to severe OSA (MSO), very severe OSA (VSO), and very severe OSA patients on long-term continuous positive airway pressure treatment (VSOC). Comparisons of the microarray gene expression data identified eight genes up-regulated with OSA and down-regulated with CPAP treatment, and five genes down-regulated with OSA and up-regulated with CPAP treatment. Protein expression levels of two genes related to endothelial tight junction (AMOT P130, and PLEKHH3), and three genes related to anti-or pro-apoptosis (BIRC3, ADAR1 P150, and LGALS3) were all increased in the VSO group, while AMOT P130 was further increased, and PLEKHH3, BIRC3, and ADAR1 P150 were all decreased in the VSOC group. Subgroup analyses revealed that AMOT P130 protein expression was increased in OSA patients with excessive daytime sleepiness, BIRC3 protein expression was decreased in OSA patients with hypertension, and LGALS3 protein expression was increased in OSA patients with chronic kidney disease. In vitro short-term intermittent hypoxia with re-oxygenation experiment showed immediate over-expression of ADAR1 P150. In conclusion, we identified a novel association between AMOT/PLEKHH3/BIRC3/ADAR1/LGALS3 over-expressions and high severity index in OSA patients. AMOT and GALIG may constitute an important determinant for the development of hypersomnia and kidney injury, respectively, while BIRC3 may play a protective role in the development of hypertension. Public Library of Science 2017-05-17 /pmc/articles/PMC5435176/ /pubmed/28520763 http://dx.doi.org/10.1371/journal.pone.0176575 Text en © 2017 Chen et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article Chen, Yung-Che Chen, Kuang-Den Su, Mao-Chang Chin, Chien-Hung Chen, Chung-Jen Liou, Chia-Wei Chen, Ting-Wen Chang, Ya-Chun Huang, Kuo-Tung Wang, Chin-Chou Wang, Ting-Ya Chang, Jen-Chieh Lin, Yong-Yong Zheng, Yi-Xin Lin, Meng-Chih Hsiao, Chang-Chun Genome-wide gene expression array identifies novel genes related to disease severity and excessive daytime sleepiness in patients with obstructive sleep apnea |
title | Genome-wide gene expression array identifies novel genes related to disease severity and excessive daytime sleepiness in patients with obstructive sleep apnea |
title_full | Genome-wide gene expression array identifies novel genes related to disease severity and excessive daytime sleepiness in patients with obstructive sleep apnea |
title_fullStr | Genome-wide gene expression array identifies novel genes related to disease severity and excessive daytime sleepiness in patients with obstructive sleep apnea |
title_full_unstemmed | Genome-wide gene expression array identifies novel genes related to disease severity and excessive daytime sleepiness in patients with obstructive sleep apnea |
title_short | Genome-wide gene expression array identifies novel genes related to disease severity and excessive daytime sleepiness in patients with obstructive sleep apnea |
title_sort | genome-wide gene expression array identifies novel genes related to disease severity and excessive daytime sleepiness in patients with obstructive sleep apnea |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5435176/ https://www.ncbi.nlm.nih.gov/pubmed/28520763 http://dx.doi.org/10.1371/journal.pone.0176575 |
work_keys_str_mv | AT chenyungche genomewidegeneexpressionarrayidentifiesnovelgenesrelatedtodiseaseseverityandexcessivedaytimesleepinessinpatientswithobstructivesleepapnea AT chenkuangden genomewidegeneexpressionarrayidentifiesnovelgenesrelatedtodiseaseseverityandexcessivedaytimesleepinessinpatientswithobstructivesleepapnea AT sumaochang genomewidegeneexpressionarrayidentifiesnovelgenesrelatedtodiseaseseverityandexcessivedaytimesleepinessinpatientswithobstructivesleepapnea AT chinchienhung genomewidegeneexpressionarrayidentifiesnovelgenesrelatedtodiseaseseverityandexcessivedaytimesleepinessinpatientswithobstructivesleepapnea AT chenchungjen genomewidegeneexpressionarrayidentifiesnovelgenesrelatedtodiseaseseverityandexcessivedaytimesleepinessinpatientswithobstructivesleepapnea AT liouchiawei genomewidegeneexpressionarrayidentifiesnovelgenesrelatedtodiseaseseverityandexcessivedaytimesleepinessinpatientswithobstructivesleepapnea AT chentingwen genomewidegeneexpressionarrayidentifiesnovelgenesrelatedtodiseaseseverityandexcessivedaytimesleepinessinpatientswithobstructivesleepapnea AT changyachun genomewidegeneexpressionarrayidentifiesnovelgenesrelatedtodiseaseseverityandexcessivedaytimesleepinessinpatientswithobstructivesleepapnea AT huangkuotung genomewidegeneexpressionarrayidentifiesnovelgenesrelatedtodiseaseseverityandexcessivedaytimesleepinessinpatientswithobstructivesleepapnea AT wangchinchou genomewidegeneexpressionarrayidentifiesnovelgenesrelatedtodiseaseseverityandexcessivedaytimesleepinessinpatientswithobstructivesleepapnea AT wangtingya genomewidegeneexpressionarrayidentifiesnovelgenesrelatedtodiseaseseverityandexcessivedaytimesleepinessinpatientswithobstructivesleepapnea AT changjenchieh genomewidegeneexpressionarrayidentifiesnovelgenesrelatedtodiseaseseverityandexcessivedaytimesleepinessinpatientswithobstructivesleepapnea AT linyongyong genomewidegeneexpressionarrayidentifiesnovelgenesrelatedtodiseaseseverityandexcessivedaytimesleepinessinpatientswithobstructivesleepapnea AT zhengyixin genomewidegeneexpressionarrayidentifiesnovelgenesrelatedtodiseaseseverityandexcessivedaytimesleepinessinpatientswithobstructivesleepapnea AT linmengchih genomewidegeneexpressionarrayidentifiesnovelgenesrelatedtodiseaseseverityandexcessivedaytimesleepinessinpatientswithobstructivesleepapnea AT hsiaochangchun genomewidegeneexpressionarrayidentifiesnovelgenesrelatedtodiseaseseverityandexcessivedaytimesleepinessinpatientswithobstructivesleepapnea |