Transcriptome analysis of controlled and therapy-resistant childhood asthma reveals distinct gene expression profiles
Background Children with problematic severe asthma have poor disease control despite high doses of inhaled corticosteroids and additional therapy, leading to personal suffering, early deterioration of lung function, and significant consumption of health care resources. If no exacerbating factors, su...
Gespeichert in:
Veröffentlicht in: | Journal of allergy and clinical immunology 2015-09, Vol.136 (3), p.638-648 |
---|---|
Hauptverfasser: | , , , , , , , , , , , , , |
Format: | Artikel |
Sprache: | eng |
Schlagworte: | |
Online-Zugang: | Volltext |
Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
container_end_page | 648 |
---|---|
container_issue | 3 |
container_start_page | 638 |
container_title | Journal of allergy and clinical immunology |
container_volume | 136 |
creator | Persson, Helena, PhD Kwon, Andrew T., PhD Ramilowski, Jordan A., PhD Silberberg, Gilad, PhD Söderhäll, Cilla, PhD Orsmark-Pietras, Christina, PhD Nordlund, Björn, RN, PhD Konradsen, Jon R., MD, PhD de Hoon, Michiel J.L., PhD Melén, Erik, MD, PhD Hayashizaki, Yoshihide, MD, PhD Hedlin, Gunilla, MD, PhD Kere, Juha, MD, PhD Daub, Carsten O., PhD |
description | Background Children with problematic severe asthma have poor disease control despite high doses of inhaled corticosteroids and additional therapy, leading to personal suffering, early deterioration of lung function, and significant consumption of health care resources. If no exacerbating factors, such as smoking or allergies, are found after extensive investigation, these children are given a diagnosis of therapy-resistant (or therapy-refractory) asthma (SA). Objective We sought to deepen our understanding of childhood SA by analyzing gene expression and modeling the underlying regulatory transcription factor networks in peripheral blood leukocytes. Methods Gene expression was analyzed by using Cap Analysis of Gene Expression in children with SA (n = 13), children with controlled persistent asthma (n = 15), and age-matched healthy control subjects (n = 9). Cap Analysis of Gene Expression sequencing detects the transcription start sites of known and novel mRNAs and noncoding RNAs. Results Sample groups could be separated by hierarchical clustering on 1305 differentially expressed transcription start sites, including 816 known genes and several novel transcripts. Ten of 13 tested novel transcripts were validated by means of RT-PCR and Sanger sequencing. Expression of RAR-related orphan receptor A (RORA) , which has been linked to asthma in genome-wide association studies, was significantly upregulated in patients with SA. Gene network modeling revealed decreased glucocorticoid receptor signaling and increased activity of the mitogen-activated protein kinase and Jun kinase cascades in patients with SA. Conclusion Circulating leukocytes from children with controlled asthma and those with SA have distinct gene expression profiles, demonstrating the possible development of specific molecular biomarkers and supporting the need for novel therapeutic approaches. |
doi_str_mv | 10.1016/j.jaci.2015.02.026 |
format | Article |
fullrecord | <record><control><sourceid>proquest_swepu</sourceid><recordid>TN_cdi_swepub_primary_oai_swepub_ki_se_514330</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><els_id>S0091674915003280</els_id><sourcerecordid>1717495323</sourcerecordid><originalsourceid>FETCH-LOGICAL-c674t-d6d8fc12db225d068561358f468a004e350cbcee94d26bd1b9c254edf6d8f9aa3</originalsourceid><addsrcrecordid>eNqNkl2L1DAUhoso7rj6B7yQgjfedMxHk2lAhGVxVVjwwvU6pMmpk26mqUm7Ov9-T5nZXVhQhEDS5HkOp5y3KF5TsqaEyvf9ujfWrxmhYk0YLvmkWFGiNpVsmHharAhRtJKbWp0UL3LuCX7zRj0vTphoJFcNXRXzVTJDtsmPU9xBaQYT9tnnMnaljcOUYgjg8NqV0xaSGfdVAnyfzDCVduuD28aI73na7kyZ4AZMyKVDwA92Kn_CACX8GdHJPg7lmGLnA-SXxbMOQXh13E-LHxefrs6_VJffPn89P7usLHY9VU66prOUuZYx4YhshKRcNF0tG0NIDVwQ21oAVTsmW0dbZZmowXWLp4zhp0V1qJt_wzi3ekx-Z9JeR-P18eoaT6AFrTknyKu_8ti7e5DuRMqpklJtGnTfHVwEf82QJ73z2UIIZoA4Z003FCchOOP_gxIpaqZqRN8-Qvs4J5zSQhHFaioVRYodKJtizgm6-84p0UtWdK-XrOglK5owXBKlN8fSc7sDd6_chQOBDwcAcEQ3HpLO1sNgwfkEdtIu-n_X__hIt8EP3ppwDXvID_-hMwr6-5LWJaxUEMJZQ_gt9svoOQ</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1709241691</pqid></control><display><type>article</type><title>Transcriptome analysis of controlled and therapy-resistant childhood asthma reveals distinct gene expression profiles</title><source>MEDLINE</source><source>SWEPUB Freely available online</source><source>Access via ScienceDirect (Elsevier)</source><source>EZB-FREE-00999 freely available EZB journals</source><creator>Persson, Helena, PhD ; Kwon, Andrew T., PhD ; Ramilowski, Jordan A., PhD ; Silberberg, Gilad, PhD ; Söderhäll, Cilla, PhD ; Orsmark-Pietras, Christina, PhD ; Nordlund, Björn, RN, PhD ; Konradsen, Jon R., MD, PhD ; de Hoon, Michiel J.L., PhD ; Melén, Erik, MD, PhD ; Hayashizaki, Yoshihide, MD, PhD ; Hedlin, Gunilla, MD, PhD ; Kere, Juha, MD, PhD ; Daub, Carsten O., PhD</creator><creatorcontrib>Persson, Helena, PhD ; Kwon, Andrew T., PhD ; Ramilowski, Jordan A., PhD ; Silberberg, Gilad, PhD ; Söderhäll, Cilla, PhD ; Orsmark-Pietras, Christina, PhD ; Nordlund, Björn, RN, PhD ; Konradsen, Jon R., MD, PhD ; de Hoon, Michiel J.L., PhD ; Melén, Erik, MD, PhD ; Hayashizaki, Yoshihide, MD, PhD ; Hedlin, Gunilla, MD, PhD ; Kere, Juha, MD, PhD ; Daub, Carsten O., PhD</creatorcontrib><description>Background Children with problematic severe asthma have poor disease control despite high doses of inhaled corticosteroids and additional therapy, leading to personal suffering, early deterioration of lung function, and significant consumption of health care resources. If no exacerbating factors, such as smoking or allergies, are found after extensive investigation, these children are given a diagnosis of therapy-resistant (or therapy-refractory) asthma (SA). Objective We sought to deepen our understanding of childhood SA by analyzing gene expression and modeling the underlying regulatory transcription factor networks in peripheral blood leukocytes. Methods Gene expression was analyzed by using Cap Analysis of Gene Expression in children with SA (n = 13), children with controlled persistent asthma (n = 15), and age-matched healthy control subjects (n = 9). Cap Analysis of Gene Expression sequencing detects the transcription start sites of known and novel mRNAs and noncoding RNAs. Results Sample groups could be separated by hierarchical clustering on 1305 differentially expressed transcription start sites, including 816 known genes and several novel transcripts. Ten of 13 tested novel transcripts were validated by means of RT-PCR and Sanger sequencing. Expression of RAR-related orphan receptor A (RORA) , which has been linked to asthma in genome-wide association studies, was significantly upregulated in patients with SA. Gene network modeling revealed decreased glucocorticoid receptor signaling and increased activity of the mitogen-activated protein kinase and Jun kinase cascades in patients with SA. Conclusion Circulating leukocytes from children with controlled asthma and those with SA have distinct gene expression profiles, demonstrating the possible development of specific molecular biomarkers and supporting the need for novel therapeutic approaches.</description><identifier>ISSN: 0091-6749</identifier><identifier>ISSN: 1097-6825</identifier><identifier>EISSN: 1097-6825</identifier><identifier>DOI: 10.1016/j.jaci.2015.02.026</identifier><identifier>PMID: 25863981</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Adolescent ; Allergy and Immunology ; Asthma ; Asthma - drug therapy ; Asthma - genetics ; Asthma - pathology ; Case-Control Studies ; Child ; Child, Preschool ; childhood asthma ; Drug Resistance - genetics ; Female ; Gene expression ; Gene Expression Profiling ; Genome-Wide Association Study ; Glucocorticoids - therapeutic use ; Humans ; JNK Mitogen-Activated Protein Kinases - genetics ; long noncoding RNA ; Male ; Medicin och hälsovetenskap ; Nuclear Receptor Subfamily 1, Group F, Member 1 - genetics ; peripheral blood leukocytes ; Receptors, Glucocorticoid - genetics ; RNA polymerase ; RNA, Messenger - genetics ; Severity of Illness Index ; Therapy-resistant asthma ; Transcriptome</subject><ispartof>Journal of allergy and clinical immunology, 2015-09, Vol.136 (3), p.638-648</ispartof><rights>The Authors</rights><rights>2015 The Authors</rights><rights>Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.</rights><rights>Copyright Elsevier Limited Sep 2015</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c674t-d6d8fc12db225d068561358f468a004e350cbcee94d26bd1b9c254edf6d8f9aa3</citedby><cites>FETCH-LOGICAL-c674t-d6d8fc12db225d068561358f468a004e350cbcee94d26bd1b9c254edf6d8f9aa3</cites><orcidid>0000-0002-3295-8729 ; 0000-0002-5187-6446</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.jaci.2015.02.026$$EHTML$$P50$$Gelsevier$$Hfree_for_read</linktohtml><link.rule.ids>230,315,553,781,785,886,3551,27929,27930,46000</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/25863981$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttp://kipublications.ki.se/Default.aspx?queryparsed=id:131966978$$DView record from Swedish Publication Index$$Hfree_for_read</backlink></links><search><creatorcontrib>Persson, Helena, PhD</creatorcontrib><creatorcontrib>Kwon, Andrew T., PhD</creatorcontrib><creatorcontrib>Ramilowski, Jordan A., PhD</creatorcontrib><creatorcontrib>Silberberg, Gilad, PhD</creatorcontrib><creatorcontrib>Söderhäll, Cilla, PhD</creatorcontrib><creatorcontrib>Orsmark-Pietras, Christina, PhD</creatorcontrib><creatorcontrib>Nordlund, Björn, RN, PhD</creatorcontrib><creatorcontrib>Konradsen, Jon R., MD, PhD</creatorcontrib><creatorcontrib>de Hoon, Michiel J.L., PhD</creatorcontrib><creatorcontrib>Melén, Erik, MD, PhD</creatorcontrib><creatorcontrib>Hayashizaki, Yoshihide, MD, PhD</creatorcontrib><creatorcontrib>Hedlin, Gunilla, MD, PhD</creatorcontrib><creatorcontrib>Kere, Juha, MD, PhD</creatorcontrib><creatorcontrib>Daub, Carsten O., PhD</creatorcontrib><title>Transcriptome analysis of controlled and therapy-resistant childhood asthma reveals distinct gene expression profiles</title><title>Journal of allergy and clinical immunology</title><addtitle>J Allergy Clin Immunol</addtitle><description>Background Children with problematic severe asthma have poor disease control despite high doses of inhaled corticosteroids and additional therapy, leading to personal suffering, early deterioration of lung function, and significant consumption of health care resources. If no exacerbating factors, such as smoking or allergies, are found after extensive investigation, these children are given a diagnosis of therapy-resistant (or therapy-refractory) asthma (SA). Objective We sought to deepen our understanding of childhood SA by analyzing gene expression and modeling the underlying regulatory transcription factor networks in peripheral blood leukocytes. Methods Gene expression was analyzed by using Cap Analysis of Gene Expression in children with SA (n = 13), children with controlled persistent asthma (n = 15), and age-matched healthy control subjects (n = 9). Cap Analysis of Gene Expression sequencing detects the transcription start sites of known and novel mRNAs and noncoding RNAs. Results Sample groups could be separated by hierarchical clustering on 1305 differentially expressed transcription start sites, including 816 known genes and several novel transcripts. Ten of 13 tested novel transcripts were validated by means of RT-PCR and Sanger sequencing. Expression of RAR-related orphan receptor A (RORA) , which has been linked to asthma in genome-wide association studies, was significantly upregulated in patients with SA. Gene network modeling revealed decreased glucocorticoid receptor signaling and increased activity of the mitogen-activated protein kinase and Jun kinase cascades in patients with SA. Conclusion Circulating leukocytes from children with controlled asthma and those with SA have distinct gene expression profiles, demonstrating the possible development of specific molecular biomarkers and supporting the need for novel therapeutic approaches.</description><subject>Adolescent</subject><subject>Allergy and Immunology</subject><subject>Asthma</subject><subject>Asthma - drug therapy</subject><subject>Asthma - genetics</subject><subject>Asthma - pathology</subject><subject>Case-Control Studies</subject><subject>Child</subject><subject>Child, Preschool</subject><subject>childhood asthma</subject><subject>Drug Resistance - genetics</subject><subject>Female</subject><subject>Gene expression</subject><subject>Gene Expression Profiling</subject><subject>Genome-Wide Association Study</subject><subject>Glucocorticoids - therapeutic use</subject><subject>Humans</subject><subject>JNK Mitogen-Activated Protein Kinases - genetics</subject><subject>long noncoding RNA</subject><subject>Male</subject><subject>Medicin och hälsovetenskap</subject><subject>Nuclear Receptor Subfamily 1, Group F, Member 1 - genetics</subject><subject>peripheral blood leukocytes</subject><subject>Receptors, Glucocorticoid - genetics</subject><subject>RNA polymerase</subject><subject>RNA, Messenger - genetics</subject><subject>Severity of Illness Index</subject><subject>Therapy-resistant asthma</subject><subject>Transcriptome</subject><issn>0091-6749</issn><issn>1097-6825</issn><issn>1097-6825</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>D8T</sourceid><recordid>eNqNkl2L1DAUhoso7rj6B7yQgjfedMxHk2lAhGVxVVjwwvU6pMmpk26mqUm7Ov9-T5nZXVhQhEDS5HkOp5y3KF5TsqaEyvf9ujfWrxmhYk0YLvmkWFGiNpVsmHharAhRtJKbWp0UL3LuCX7zRj0vTphoJFcNXRXzVTJDtsmPU9xBaQYT9tnnMnaljcOUYgjg8NqV0xaSGfdVAnyfzDCVduuD28aI73na7kyZ4AZMyKVDwA92Kn_CACX8GdHJPg7lmGLnA-SXxbMOQXh13E-LHxefrs6_VJffPn89P7usLHY9VU66prOUuZYx4YhshKRcNF0tG0NIDVwQ21oAVTsmW0dbZZmowXWLp4zhp0V1qJt_wzi3ekx-Z9JeR-P18eoaT6AFrTknyKu_8ti7e5DuRMqpklJtGnTfHVwEf82QJ73z2UIIZoA4Z003FCchOOP_gxIpaqZqRN8-Qvs4J5zSQhHFaioVRYodKJtizgm6-84p0UtWdK-XrOglK5owXBKlN8fSc7sDd6_chQOBDwcAcEQ3HpLO1sNgwfkEdtIu-n_X__hIt8EP3ppwDXvID_-hMwr6-5LWJaxUEMJZQ_gt9svoOQ</recordid><startdate>20150901</startdate><enddate>20150901</enddate><creator>Persson, Helena, PhD</creator><creator>Kwon, Andrew T., PhD</creator><creator>Ramilowski, Jordan A., PhD</creator><creator>Silberberg, Gilad, PhD</creator><creator>Söderhäll, Cilla, PhD</creator><creator>Orsmark-Pietras, Christina, PhD</creator><creator>Nordlund, Björn, RN, PhD</creator><creator>Konradsen, Jon R., MD, PhD</creator><creator>de Hoon, Michiel J.L., PhD</creator><creator>Melén, Erik, MD, PhD</creator><creator>Hayashizaki, Yoshihide, MD, PhD</creator><creator>Hedlin, Gunilla, MD, PhD</creator><creator>Kere, Juha, MD, PhD</creator><creator>Daub, Carsten O., PhD</creator><general>Elsevier Inc</general><general>Elsevier Limited</general><scope>6I.</scope><scope>AAFTH</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7SS</scope><scope>7T5</scope><scope>H94</scope><scope>K9.</scope><scope>NAPCQ</scope><scope>7X8</scope><scope>ADTPV</scope><scope>AOWAS</scope><scope>D8T</scope><scope>ZZAVC</scope><orcidid>https://orcid.org/0000-0002-3295-8729</orcidid><orcidid>https://orcid.org/0000-0002-5187-6446</orcidid></search><sort><creationdate>20150901</creationdate><title>Transcriptome analysis of controlled and therapy-resistant childhood asthma reveals distinct gene expression profiles</title><author>Persson, Helena, PhD ; Kwon, Andrew T., PhD ; Ramilowski, Jordan A., PhD ; Silberberg, Gilad, PhD ; Söderhäll, Cilla, PhD ; Orsmark-Pietras, Christina, PhD ; Nordlund, Björn, RN, PhD ; Konradsen, Jon R., MD, PhD ; de Hoon, Michiel J.L., PhD ; Melén, Erik, MD, PhD ; Hayashizaki, Yoshihide, MD, PhD ; Hedlin, Gunilla, MD, PhD ; Kere, Juha, MD, PhD ; Daub, Carsten O., PhD</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c674t-d6d8fc12db225d068561358f468a004e350cbcee94d26bd1b9c254edf6d8f9aa3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>Adolescent</topic><topic>Allergy and Immunology</topic><topic>Asthma</topic><topic>Asthma - drug therapy</topic><topic>Asthma - genetics</topic><topic>Asthma - pathology</topic><topic>Case-Control Studies</topic><topic>Child</topic><topic>Child, Preschool</topic><topic>childhood asthma</topic><topic>Drug Resistance - genetics</topic><topic>Female</topic><topic>Gene expression</topic><topic>Gene Expression Profiling</topic><topic>Genome-Wide Association Study</topic><topic>Glucocorticoids - therapeutic use</topic><topic>Humans</topic><topic>JNK Mitogen-Activated Protein Kinases - genetics</topic><topic>long noncoding RNA</topic><topic>Male</topic><topic>Medicin och hälsovetenskap</topic><topic>Nuclear Receptor Subfamily 1, Group F, Member 1 - genetics</topic><topic>peripheral blood leukocytes</topic><topic>Receptors, Glucocorticoid - genetics</topic><topic>RNA polymerase</topic><topic>RNA, Messenger - genetics</topic><topic>Severity of Illness Index</topic><topic>Therapy-resistant asthma</topic><topic>Transcriptome</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Persson, Helena, PhD</creatorcontrib><creatorcontrib>Kwon, Andrew T., PhD</creatorcontrib><creatorcontrib>Ramilowski, Jordan A., PhD</creatorcontrib><creatorcontrib>Silberberg, Gilad, PhD</creatorcontrib><creatorcontrib>Söderhäll, Cilla, PhD</creatorcontrib><creatorcontrib>Orsmark-Pietras, Christina, PhD</creatorcontrib><creatorcontrib>Nordlund, Björn, RN, PhD</creatorcontrib><creatorcontrib>Konradsen, Jon R., MD, PhD</creatorcontrib><creatorcontrib>de Hoon, Michiel J.L., PhD</creatorcontrib><creatorcontrib>Melén, Erik, MD, PhD</creatorcontrib><creatorcontrib>Hayashizaki, Yoshihide, MD, PhD</creatorcontrib><creatorcontrib>Hedlin, Gunilla, MD, PhD</creatorcontrib><creatorcontrib>Kere, Juha, MD, PhD</creatorcontrib><creatorcontrib>Daub, Carsten O., PhD</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Immunology Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Premium</collection><collection>MEDLINE - Academic</collection><collection>SwePub</collection><collection>SwePub Articles</collection><collection>SWEPUB Freely available online</collection><collection>SwePub Articles full text</collection><jtitle>Journal of allergy and clinical immunology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Persson, Helena, PhD</au><au>Kwon, Andrew T., PhD</au><au>Ramilowski, Jordan A., PhD</au><au>Silberberg, Gilad, PhD</au><au>Söderhäll, Cilla, PhD</au><au>Orsmark-Pietras, Christina, PhD</au><au>Nordlund, Björn, RN, PhD</au><au>Konradsen, Jon R., MD, PhD</au><au>de Hoon, Michiel J.L., PhD</au><au>Melén, Erik, MD, PhD</au><au>Hayashizaki, Yoshihide, MD, PhD</au><au>Hedlin, Gunilla, MD, PhD</au><au>Kere, Juha, MD, PhD</au><au>Daub, Carsten O., PhD</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Transcriptome analysis of controlled and therapy-resistant childhood asthma reveals distinct gene expression profiles</atitle><jtitle>Journal of allergy and clinical immunology</jtitle><addtitle>J Allergy Clin Immunol</addtitle><date>2015-09-01</date><risdate>2015</risdate><volume>136</volume><issue>3</issue><spage>638</spage><epage>648</epage><pages>638-648</pages><issn>0091-6749</issn><issn>1097-6825</issn><eissn>1097-6825</eissn><abstract>Background Children with problematic severe asthma have poor disease control despite high doses of inhaled corticosteroids and additional therapy, leading to personal suffering, early deterioration of lung function, and significant consumption of health care resources. If no exacerbating factors, such as smoking or allergies, are found after extensive investigation, these children are given a diagnosis of therapy-resistant (or therapy-refractory) asthma (SA). Objective We sought to deepen our understanding of childhood SA by analyzing gene expression and modeling the underlying regulatory transcription factor networks in peripheral blood leukocytes. Methods Gene expression was analyzed by using Cap Analysis of Gene Expression in children with SA (n = 13), children with controlled persistent asthma (n = 15), and age-matched healthy control subjects (n = 9). Cap Analysis of Gene Expression sequencing detects the transcription start sites of known and novel mRNAs and noncoding RNAs. Results Sample groups could be separated by hierarchical clustering on 1305 differentially expressed transcription start sites, including 816 known genes and several novel transcripts. Ten of 13 tested novel transcripts were validated by means of RT-PCR and Sanger sequencing. Expression of RAR-related orphan receptor A (RORA) , which has been linked to asthma in genome-wide association studies, was significantly upregulated in patients with SA. Gene network modeling revealed decreased glucocorticoid receptor signaling and increased activity of the mitogen-activated protein kinase and Jun kinase cascades in patients with SA. Conclusion Circulating leukocytes from children with controlled asthma and those with SA have distinct gene expression profiles, demonstrating the possible development of specific molecular biomarkers and supporting the need for novel therapeutic approaches.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>25863981</pmid><doi>10.1016/j.jaci.2015.02.026</doi><tpages>11</tpages><orcidid>https://orcid.org/0000-0002-3295-8729</orcidid><orcidid>https://orcid.org/0000-0002-5187-6446</orcidid><oa>free_for_read</oa></addata></record> |
fulltext | fulltext |
identifier | ISSN: 0091-6749 |
ispartof | Journal of allergy and clinical immunology, 2015-09, Vol.136 (3), p.638-648 |
issn | 0091-6749 1097-6825 1097-6825 |
language | eng |
recordid | cdi_swepub_primary_oai_swepub_ki_se_514330 |
source | MEDLINE; SWEPUB Freely available online; Access via ScienceDirect (Elsevier); EZB-FREE-00999 freely available EZB journals |
subjects | Adolescent Allergy and Immunology Asthma Asthma - drug therapy Asthma - genetics Asthma - pathology Case-Control Studies Child Child, Preschool childhood asthma Drug Resistance - genetics Female Gene expression Gene Expression Profiling Genome-Wide Association Study Glucocorticoids - therapeutic use Humans JNK Mitogen-Activated Protein Kinases - genetics long noncoding RNA Male Medicin och hälsovetenskap Nuclear Receptor Subfamily 1, Group F, Member 1 - genetics peripheral blood leukocytes Receptors, Glucocorticoid - genetics RNA polymerase RNA, Messenger - genetics Severity of Illness Index Therapy-resistant asthma Transcriptome |
title | Transcriptome analysis of controlled and therapy-resistant childhood asthma reveals distinct gene expression profiles |
url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-09T21%3A19%3A35IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_swepu&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Transcriptome%20analysis%20of%20controlled%20and%20therapy-resistant%20childhood%20asthma%20reveals%20distinct%20gene%20expression%20profiles&rft.jtitle=Journal%20of%20allergy%20and%20clinical%20immunology&rft.au=Persson,%20Helena,%20PhD&rft.date=2015-09-01&rft.volume=136&rft.issue=3&rft.spage=638&rft.epage=648&rft.pages=638-648&rft.issn=0091-6749&rft.eissn=1097-6825&rft_id=info:doi/10.1016/j.jaci.2015.02.026&rft_dat=%3Cproquest_swepu%3E1717495323%3C/proquest_swepu%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1709241691&rft_id=info:pmid/25863981&rft_els_id=S0091674915003280&rfr_iscdi=true |