Reduced CDHR3 expression in children wheezing with rhinovirus

Background Rhinovirus‐induced wheezing in young children has been associated with increased asthma risk at school age. Recently, the transmembrane protein cadherin‐related family member 3 (CDHR3) was identified as the RV‐C receptor and the genetic variant rs6967330 (p.Cys529Tyr) was reported to be a...

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Veröffentlicht in:Pediatric allergy and immunology 2018-03, Vol.29 (2), p.200-206
Hauptverfasser: Stenberg Hammar, Katarina, Niespodziana, Katarzyna, van Hage, Marianne, Kere, Juha, Valenta, Rudolf, Hedlin, Gunilla, Söderhäll, Cilla
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container_end_page 206
container_issue 2
container_start_page 200
container_title Pediatric allergy and immunology
container_volume 29
creator Stenberg Hammar, Katarina
Niespodziana, Katarzyna
van Hage, Marianne
Kere, Juha
Valenta, Rudolf
Hedlin, Gunilla
Söderhäll, Cilla
description Background Rhinovirus‐induced wheezing in young children has been associated with increased asthma risk at school age. Recently, the transmembrane protein cadherin‐related family member 3 (CDHR3) was identified as the RV‐C receptor and the genetic variant rs6967330 (p.Cys529Tyr) was reported to be associated with enhanced RV‐C binding and increased replication in vitro. The aim of this study was to examine rs6967330 genotypes and mRNA expression of CDHR3 in relation to presence of rhinovirus and clinical symptoms in children with acute wheezing and compare to a group of age‐matched healthy children. Methods rs6967330;G>A was genotyped (n = 216), and CDHR3 mRNA expression was measured in peripheral blood leukocytes (n = 69) from a subgroup of children wheezing with RV infection acute and at a follow‐up visit 2‐3 months later, and in healthy controls. Standardized TaqMan assays were used. Results The risk allele rs6967330‐A was over‐represented in the wheezing group (P 
doi_str_mv 10.1111/pai.12858
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Recently, the transmembrane protein cadherin‐related family member 3 (CDHR3) was identified as the RV‐C receptor and the genetic variant rs6967330 (p.Cys529Tyr) was reported to be associated with enhanced RV‐C binding and increased replication in vitro. The aim of this study was to examine rs6967330 genotypes and mRNA expression of CDHR3 in relation to presence of rhinovirus and clinical symptoms in children with acute wheezing and compare to a group of age‐matched healthy children. Methods rs6967330;G&gt;A was genotyped (n = 216), and CDHR3 mRNA expression was measured in peripheral blood leukocytes (n = 69) from a subgroup of children wheezing with RV infection acute and at a follow‐up visit 2‐3 months later, and in healthy controls. Standardized TaqMan assays were used. Results The risk allele rs6967330‐A was over‐represented in the wheezing group (P &lt; .001). Reduced mRNA levels of CDHR3 were found in children with acute wheezing as compared to the control group (P = .001). Children with the rs6967330 genotypes AA/AG showed the largest differences in CDHR3 expression between acute and follow‐up visit (P &lt; .04). Conclusions Preschool children with RV‐induced wheezing were shown to have reduced CDHR3 mRNA levels, which might result in an increased permeability of the epithelial layers of the airways and thereby an increased vulnerability. Thus, measuring CDHR3 mRNA levels might help to identify a more severe phenotype of wheezing preschool children.</description><identifier>ISSN: 0905-6157</identifier><identifier>EISSN: 1399-3038</identifier><identifier>DOI: 10.1111/pai.12858</identifier><identifier>PMID: 29314338</identifier><language>eng</language><publisher>England: Wiley Subscription Services, Inc</publisher><subject>acute wheezing ; Asthma ; Cadherins ; Cadherins - metabolism ; cadherin‐related family member 3 ; Child, Preschool ; Children ; Female ; Gene expression ; Gene Frequency ; Genetic diversity ; Genetic Predisposition to Disease ; Genetic variance ; Genotype ; Genotypes ; Humans ; Infant ; Leukocytes ; Longitudinal Studies ; Male ; Membrane Proteins - metabolism ; mRNA expression ; Peripheral blood ; peripheral blood leukocytes ; Permeability ; Phenotypes ; Picornaviridae Infections - metabolism ; Preschool children ; Respiratory Sounds - genetics ; Rhinovirus ; Rhinovirus - genetics ; Risk ; rs6967330 ; Wheezing</subject><ispartof>Pediatric allergy and immunology, 2018-03, Vol.29 (2), p.200-206</ispartof><rights>2018 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.</rights><rights>Copyright © 2018 John Wiley &amp; Sons A/S</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><orcidid>0000-0002-5185-8280 ; 0000-0002-8397-3080</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1111%2Fpai.12858$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1111%2Fpai.12858$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>230,314,776,780,881,1411,27901,27902,45550,45551</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/29314338$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttp://kipublications.ki.se/Default.aspx?queryparsed=id:137801213$$DView record from Swedish Publication Index$$Hfree_for_read</backlink></links><search><creatorcontrib>Stenberg Hammar, Katarina</creatorcontrib><creatorcontrib>Niespodziana, Katarzyna</creatorcontrib><creatorcontrib>van Hage, Marianne</creatorcontrib><creatorcontrib>Kere, Juha</creatorcontrib><creatorcontrib>Valenta, Rudolf</creatorcontrib><creatorcontrib>Hedlin, Gunilla</creatorcontrib><creatorcontrib>Söderhäll, Cilla</creatorcontrib><title>Reduced CDHR3 expression in children wheezing with rhinovirus</title><title>Pediatric allergy and immunology</title><addtitle>Pediatr Allergy Immunol</addtitle><description>Background Rhinovirus‐induced wheezing in young children has been associated with increased asthma risk at school age. Recently, the transmembrane protein cadherin‐related family member 3 (CDHR3) was identified as the RV‐C receptor and the genetic variant rs6967330 (p.Cys529Tyr) was reported to be associated with enhanced RV‐C binding and increased replication in vitro. The aim of this study was to examine rs6967330 genotypes and mRNA expression of CDHR3 in relation to presence of rhinovirus and clinical symptoms in children with acute wheezing and compare to a group of age‐matched healthy children. Methods rs6967330;G&gt;A was genotyped (n = 216), and CDHR3 mRNA expression was measured in peripheral blood leukocytes (n = 69) from a subgroup of children wheezing with RV infection acute and at a follow‐up visit 2‐3 months later, and in healthy controls. Standardized TaqMan assays were used. Results The risk allele rs6967330‐A was over‐represented in the wheezing group (P &lt; .001). Reduced mRNA levels of CDHR3 were found in children with acute wheezing as compared to the control group (P = .001). Children with the rs6967330 genotypes AA/AG showed the largest differences in CDHR3 expression between acute and follow‐up visit (P &lt; .04). Conclusions Preschool children with RV‐induced wheezing were shown to have reduced CDHR3 mRNA levels, which might result in an increased permeability of the epithelial layers of the airways and thereby an increased vulnerability. Thus, measuring CDHR3 mRNA levels might help to identify a more severe phenotype of wheezing preschool children.</description><subject>acute wheezing</subject><subject>Asthma</subject><subject>Cadherins</subject><subject>Cadherins - metabolism</subject><subject>cadherin‐related family member 3</subject><subject>Child, Preschool</subject><subject>Children</subject><subject>Female</subject><subject>Gene expression</subject><subject>Gene Frequency</subject><subject>Genetic diversity</subject><subject>Genetic Predisposition to Disease</subject><subject>Genetic variance</subject><subject>Genotype</subject><subject>Genotypes</subject><subject>Humans</subject><subject>Infant</subject><subject>Leukocytes</subject><subject>Longitudinal Studies</subject><subject>Male</subject><subject>Membrane Proteins - metabolism</subject><subject>mRNA expression</subject><subject>Peripheral blood</subject><subject>peripheral blood leukocytes</subject><subject>Permeability</subject><subject>Phenotypes</subject><subject>Picornaviridae Infections - metabolism</subject><subject>Preschool children</subject><subject>Respiratory Sounds - genetics</subject><subject>Rhinovirus</subject><subject>Rhinovirus - genetics</subject><subject>Risk</subject><subject>rs6967330</subject><subject>Wheezing</subject><issn>0905-6157</issn><issn>1399-3038</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2018</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpdkUtPwzAMxyMEYuNx4AugSly4dMR1myYHDmg8hjQJNME56sOjGV1bmpUxPj1hGzvgiy37J7_-jJ0BH4CzqyYxAwhkJPdYH1ApHznKfdbnike-gCjusSNrZ5xDjAIOWS9QCCGi7LPrCeVdRrk3vB1N0KOvpiVrTV15pvKywpR5S5W3LIi-TfXmLc2i8NrCVPWnaTt7wg6mSWnpdOuP2ev93ctw5I-fHh6HN2O_QYiln2VxQCKSoQIMpciliGKIKQx4iglgmuJUySnlqciBUhWCwCRMhTspUVIA4jHzN33tkpou1U1r5km70nVi9Db17iLSvxOkdPzlhm_a-qMju9BzYzMqy6SiurMalFSRCCDgDr34h87qrq3cNTrgwAUqt4ajzrdUl84p3y3w90gHXG2ApSlptasD178KaaeQXiukn28e1wH-ADfAgJU</recordid><startdate>201803</startdate><enddate>201803</enddate><creator>Stenberg Hammar, Katarina</creator><creator>Niespodziana, Katarzyna</creator><creator>van Hage, Marianne</creator><creator>Kere, Juha</creator><creator>Valenta, Rudolf</creator><creator>Hedlin, Gunilla</creator><creator>Söderhäll, Cilla</creator><general>Wiley Subscription Services, Inc</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>7T5</scope><scope>H94</scope><scope>K9.</scope><scope>NAPCQ</scope><scope>7X8</scope><scope>ADTPV</scope><scope>AOWAS</scope><orcidid>https://orcid.org/0000-0002-5185-8280</orcidid><orcidid>https://orcid.org/0000-0002-8397-3080</orcidid></search><sort><creationdate>201803</creationdate><title>Reduced CDHR3 expression in children wheezing with rhinovirus</title><author>Stenberg Hammar, Katarina ; Niespodziana, Katarzyna ; van Hage, Marianne ; Kere, Juha ; Valenta, Rudolf ; Hedlin, Gunilla ; Söderhäll, Cilla</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-p3178-cc72e6584913486d865717e420b3a13bb3f98fedb6d1eb94163a4b6128a986133</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2018</creationdate><topic>acute wheezing</topic><topic>Asthma</topic><topic>Cadherins</topic><topic>Cadherins - metabolism</topic><topic>cadherin‐related family member 3</topic><topic>Child, Preschool</topic><topic>Children</topic><topic>Female</topic><topic>Gene expression</topic><topic>Gene Frequency</topic><topic>Genetic diversity</topic><topic>Genetic Predisposition to Disease</topic><topic>Genetic variance</topic><topic>Genotype</topic><topic>Genotypes</topic><topic>Humans</topic><topic>Infant</topic><topic>Leukocytes</topic><topic>Longitudinal Studies</topic><topic>Male</topic><topic>Membrane Proteins - metabolism</topic><topic>mRNA expression</topic><topic>Peripheral blood</topic><topic>peripheral blood leukocytes</topic><topic>Permeability</topic><topic>Phenotypes</topic><topic>Picornaviridae Infections - metabolism</topic><topic>Preschool children</topic><topic>Respiratory Sounds - genetics</topic><topic>Rhinovirus</topic><topic>Rhinovirus - genetics</topic><topic>Risk</topic><topic>rs6967330</topic><topic>Wheezing</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Stenberg Hammar, Katarina</creatorcontrib><creatorcontrib>Niespodziana, Katarzyna</creatorcontrib><creatorcontrib>van Hage, Marianne</creatorcontrib><creatorcontrib>Kere, Juha</creatorcontrib><creatorcontrib>Valenta, Rudolf</creatorcontrib><creatorcontrib>Hedlin, Gunilla</creatorcontrib><creatorcontrib>Söderhäll, Cilla</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>Immunology Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health &amp; Medical Complete (Alumni)</collection><collection>Nursing &amp; Allied Health Premium</collection><collection>MEDLINE - Academic</collection><collection>SwePub</collection><collection>SwePub Articles</collection><jtitle>Pediatric allergy and immunology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Stenberg Hammar, Katarina</au><au>Niespodziana, Katarzyna</au><au>van Hage, Marianne</au><au>Kere, Juha</au><au>Valenta, Rudolf</au><au>Hedlin, Gunilla</au><au>Söderhäll, Cilla</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Reduced CDHR3 expression in children wheezing with rhinovirus</atitle><jtitle>Pediatric allergy and immunology</jtitle><addtitle>Pediatr Allergy Immunol</addtitle><date>2018-03</date><risdate>2018</risdate><volume>29</volume><issue>2</issue><spage>200</spage><epage>206</epage><pages>200-206</pages><issn>0905-6157</issn><eissn>1399-3038</eissn><abstract>Background Rhinovirus‐induced wheezing in young children has been associated with increased asthma risk at school age. Recently, the transmembrane protein cadherin‐related family member 3 (CDHR3) was identified as the RV‐C receptor and the genetic variant rs6967330 (p.Cys529Tyr) was reported to be associated with enhanced RV‐C binding and increased replication in vitro. The aim of this study was to examine rs6967330 genotypes and mRNA expression of CDHR3 in relation to presence of rhinovirus and clinical symptoms in children with acute wheezing and compare to a group of age‐matched healthy children. Methods rs6967330;G&gt;A was genotyped (n = 216), and CDHR3 mRNA expression was measured in peripheral blood leukocytes (n = 69) from a subgroup of children wheezing with RV infection acute and at a follow‐up visit 2‐3 months later, and in healthy controls. Standardized TaqMan assays were used. Results The risk allele rs6967330‐A was over‐represented in the wheezing group (P &lt; .001). Reduced mRNA levels of CDHR3 were found in children with acute wheezing as compared to the control group (P = .001). Children with the rs6967330 genotypes AA/AG showed the largest differences in CDHR3 expression between acute and follow‐up visit (P &lt; .04). Conclusions Preschool children with RV‐induced wheezing were shown to have reduced CDHR3 mRNA levels, which might result in an increased permeability of the epithelial layers of the airways and thereby an increased vulnerability. Thus, measuring CDHR3 mRNA levels might help to identify a more severe phenotype of wheezing preschool children.</abstract><cop>England</cop><pub>Wiley Subscription Services, Inc</pub><pmid>29314338</pmid><doi>10.1111/pai.12858</doi><tpages>7</tpages><orcidid>https://orcid.org/0000-0002-5185-8280</orcidid><orcidid>https://orcid.org/0000-0002-8397-3080</orcidid></addata></record>
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source MEDLINE; Wiley Online Library Journals Frontfile Complete
subjects acute wheezing
Asthma
Cadherins
Cadherins - metabolism
cadherin‐related family member 3
Child, Preschool
Children
Female
Gene expression
Gene Frequency
Genetic diversity
Genetic Predisposition to Disease
Genetic variance
Genotype
Genotypes
Humans
Infant
Leukocytes
Longitudinal Studies
Male
Membrane Proteins - metabolism
mRNA expression
Peripheral blood
peripheral blood leukocytes
Permeability
Phenotypes
Picornaviridae Infections - metabolism
Preschool children
Respiratory Sounds - genetics
Rhinovirus
Rhinovirus - genetics
Risk
rs6967330
Wheezing
title Reduced CDHR3 expression in children wheezing with rhinovirus
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