Increased decidual mRNA expression levels of candidate maternal pre-eclampsia susceptibility genes are associated with clinical severity

Abstract Introduction Pre-eclampsia (PE) has a familial association, with daughters of women who had PE during pregnancy having more than twice the risk of developing PE themselves. Through genome-wide linkage and genetic association studies in PE-affected families and large population samples, we p...

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Veröffentlicht in:Placenta (Eastbourne) 2014-02, Vol.35 (2), p.117-124
Hauptverfasser: Yong, H.E.J, Murthi, P, Borg, A, Kalionis, B, Moses, E.K, Brennecke, S.P, Keogh, R.J
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container_end_page 124
container_issue 2
container_start_page 117
container_title Placenta (Eastbourne)
container_volume 35
creator Yong, H.E.J
Murthi, P
Borg, A
Kalionis, B
Moses, E.K
Brennecke, S.P
Keogh, R.J
description Abstract Introduction Pre-eclampsia (PE) has a familial association, with daughters of women who had PE during pregnancy having more than twice the risk of developing PE themselves. Through genome-wide linkage and genetic association studies in PE-affected families and large population samples, we previously identified the following as positional candidate maternal susceptibility genes for PE; ACVR1 , INHA , INHBB , ERAP1 , ERAP2 , LNPEP , COL4A1 and COL4A2 . The aims of this study were to determine mRNA expression levels of previously identified candidate maternal pre-eclampsia susceptibility genes from normotensive and severe PE (SPE) pregnancies and correlate mRNA expression levels with the clinical severity of SPE. Methods Third trimester decidual tissues were collected from both normotensive ( n  = 21) and SPE pregnancies ( n  = 24) and mRNA expression levels were determined by real-time PCR. Gene expression was then correlated with several parameters of clinical severity in SPE. Statistical significance was determined by Mann–Whitney U test and Spearman's Correlation. Results The data demonstrate significantly increased decidual mRNA expression levels of ACVR1 , INHBB , ERAP1 , ERAP2 , LNPEP , COL4A1 and COL4A2 in SPE ( p  
doi_str_mv 10.1016/j.placenta.2013.11.008
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Through genome-wide linkage and genetic association studies in PE-affected families and large population samples, we previously identified the following as positional candidate maternal susceptibility genes for PE; ACVR1 , INHA , INHBB , ERAP1 , ERAP2 , LNPEP , COL4A1 and COL4A2 . The aims of this study were to determine mRNA expression levels of previously identified candidate maternal pre-eclampsia susceptibility genes from normotensive and severe PE (SPE) pregnancies and correlate mRNA expression levels with the clinical severity of SPE. Methods Third trimester decidual tissues were collected from both normotensive ( n  = 21) and SPE pregnancies ( n  = 24) and mRNA expression levels were determined by real-time PCR. Gene expression was then correlated with several parameters of clinical severity in SPE. Statistical significance was determined by Mann–Whitney U test and Spearman's Correlation. Results The data demonstrate significantly increased decidual mRNA expression levels of ACVR1 , INHBB , ERAP1 , ERAP2 , LNPEP , COL4A1 and COL4A2 in SPE ( p  &lt; 0.05). Increased mRNA expression levels of several genes – INHA , INHBB , COL4A1 and COL4A2 were correlated with earlier onset of PE and earlier delivery of the fetus ( p  &lt; 0.05). Conclusion These results suggest altered expression of maternal susceptibility genes may play roles in PE development and the course of disease severity.</description><identifier>ISSN: 0143-4004</identifier><identifier>EISSN: 1532-3102</identifier><identifier>DOI: 10.1016/j.placenta.2013.11.008</identifier><identifier>PMID: 24331737</identifier><language>eng</language><publisher>Netherlands: Elsevier Ltd</publisher><subject>Activin Receptors, Type I - biosynthesis ; Adult ; Clinical severity ; Collagen Type IV - biosynthesis ; Decidua ; Decidua - metabolism ; Female ; Gene expression ; Genetic Predisposition to Disease - genetics ; Humans ; Inhibin-beta Subunits - biosynthesis ; Inhibins - biosynthesis ; Internal Medicine ; Obstetrics and Gynecology ; Pre-eclampsia ; Pre-Eclampsia - genetics ; Pre-Eclampsia - metabolism ; Pregnancy ; Pregnancy Trimester, Third ; RNA, Messenger - metabolism ; Susceptibility genes</subject><ispartof>Placenta (Eastbourne), 2014-02, Vol.35 (2), p.117-124</ispartof><rights>Elsevier Ltd</rights><rights>2013 Elsevier Ltd</rights><rights>Copyright © 2013 Elsevier Ltd. All rights reserved.</rights><rights>2013 Elsevier Ltd. All rights reserved. 2013</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4418-24141a2df1ae1e192dba27b27f753414bd56ec8d69eec907df5cbf076ee6835f3</citedby><cites>FETCH-LOGICAL-c4418-24141a2df1ae1e192dba27b27f753414bd56ec8d69eec907df5cbf076ee6835f3</cites><orcidid>0000-0002-8814-752X ; 0000-0002-4025-5257</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.placenta.2013.11.008$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>230,314,780,784,885,3550,27924,27925,45995</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/24331737$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Yong, H.E.J</creatorcontrib><creatorcontrib>Murthi, P</creatorcontrib><creatorcontrib>Borg, A</creatorcontrib><creatorcontrib>Kalionis, B</creatorcontrib><creatorcontrib>Moses, E.K</creatorcontrib><creatorcontrib>Brennecke, S.P</creatorcontrib><creatorcontrib>Keogh, R.J</creatorcontrib><title>Increased decidual mRNA expression levels of candidate maternal pre-eclampsia susceptibility genes are associated with clinical severity</title><title>Placenta (Eastbourne)</title><addtitle>Placenta</addtitle><description>Abstract Introduction Pre-eclampsia (PE) has a familial association, with daughters of women who had PE during pregnancy having more than twice the risk of developing PE themselves. Through genome-wide linkage and genetic association studies in PE-affected families and large population samples, we previously identified the following as positional candidate maternal susceptibility genes for PE; ACVR1 , INHA , INHBB , ERAP1 , ERAP2 , LNPEP , COL4A1 and COL4A2 . The aims of this study were to determine mRNA expression levels of previously identified candidate maternal pre-eclampsia susceptibility genes from normotensive and severe PE (SPE) pregnancies and correlate mRNA expression levels with the clinical severity of SPE. Methods Third trimester decidual tissues were collected from both normotensive ( n  = 21) and SPE pregnancies ( n  = 24) and mRNA expression levels were determined by real-time PCR. Gene expression was then correlated with several parameters of clinical severity in SPE. Statistical significance was determined by Mann–Whitney U test and Spearman's Correlation. Results The data demonstrate significantly increased decidual mRNA expression levels of ACVR1 , INHBB , ERAP1 , ERAP2 , LNPEP , COL4A1 and COL4A2 in SPE ( p  &lt; 0.05). Increased mRNA expression levels of several genes – INHA , INHBB , COL4A1 and COL4A2 were correlated with earlier onset of PE and earlier delivery of the fetus ( p  &lt; 0.05). Conclusion These results suggest altered expression of maternal susceptibility genes may play roles in PE development and the course of disease severity.</description><subject>Activin Receptors, Type I - biosynthesis</subject><subject>Adult</subject><subject>Clinical severity</subject><subject>Collagen Type IV - biosynthesis</subject><subject>Decidua</subject><subject>Decidua - metabolism</subject><subject>Female</subject><subject>Gene expression</subject><subject>Genetic Predisposition to Disease - genetics</subject><subject>Humans</subject><subject>Inhibin-beta Subunits - biosynthesis</subject><subject>Inhibins - biosynthesis</subject><subject>Internal Medicine</subject><subject>Obstetrics and Gynecology</subject><subject>Pre-eclampsia</subject><subject>Pre-Eclampsia - genetics</subject><subject>Pre-Eclampsia - metabolism</subject><subject>Pregnancy</subject><subject>Pregnancy Trimester, Third</subject><subject>RNA, Messenger - metabolism</subject><subject>Susceptibility genes</subject><issn>0143-4004</issn><issn>1532-3102</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2014</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkstuFDEQRVsIRIbAL0ResunBZXv6sYmIogCRIpB4SOwst12deHA_cHUPzB_w2bg1mQjYsLEXvveWq05l2RnwNXAoXm3XYzAW-8msBQe5BlhzXj3KVrCRIpfAxeNsxUHJXHGuTrJnRFvOea1APM1OhJISSlmusl_XvY1oCB1zaL2bTWDdx_cXDH-OEYn80LOAOwzEhpZZ0zvvzISsS0fskzipcrTBdCN5w2gmi-PkGx_8tGe32CMxE5EZosH6ZHLsh5_umA2-9zb5KYXHpH2ePWlNIHxxf59mX95cfb58l998eHt9eXGTW6WgyoUCBUa4FgwCQi1cY0TZiLItNzK9NW5ToK1cUSPampeu3dim5WWBWFRy08rT7PyQO85Nh24ZYTRBj9F3Ju71YLz--6X3d_p22GkFvBS8TAEv7wPi8H1GmnTnU9MhmB6HmTSougaZhl4naXGQ2jgQRWwfygDXC0a91UeMesGoAXTCmIxnf37ywXbklgSvD4IEBnceoybrsbfofEQ7aTf4_9c4_yfiyOQb7pG2w7zwTf1oEprrT8syLbu09FaJ6qv8DSc-y5E</recordid><startdate>201402</startdate><enddate>201402</enddate><creator>Yong, H.E.J</creator><creator>Murthi, P</creator><creator>Borg, A</creator><creator>Kalionis, B</creator><creator>Moses, E.K</creator><creator>Brennecke, S.P</creator><creator>Keogh, R.J</creator><general>Elsevier Ltd</general><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>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0002-8814-752X</orcidid><orcidid>https://orcid.org/0000-0002-4025-5257</orcidid></search><sort><creationdate>201402</creationdate><title>Increased decidual mRNA expression levels of candidate maternal pre-eclampsia susceptibility genes are associated with clinical severity</title><author>Yong, H.E.J ; Murthi, P ; Borg, A ; Kalionis, B ; Moses, E.K ; Brennecke, S.P ; Keogh, R.J</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4418-24141a2df1ae1e192dba27b27f753414bd56ec8d69eec907df5cbf076ee6835f3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2014</creationdate><topic>Activin Receptors, Type I - biosynthesis</topic><topic>Adult</topic><topic>Clinical severity</topic><topic>Collagen Type IV - biosynthesis</topic><topic>Decidua</topic><topic>Decidua - metabolism</topic><topic>Female</topic><topic>Gene expression</topic><topic>Genetic Predisposition to Disease - genetics</topic><topic>Humans</topic><topic>Inhibin-beta Subunits - biosynthesis</topic><topic>Inhibins - biosynthesis</topic><topic>Internal Medicine</topic><topic>Obstetrics and Gynecology</topic><topic>Pre-eclampsia</topic><topic>Pre-Eclampsia - genetics</topic><topic>Pre-Eclampsia - metabolism</topic><topic>Pregnancy</topic><topic>Pregnancy Trimester, Third</topic><topic>RNA, Messenger - metabolism</topic><topic>Susceptibility genes</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Yong, H.E.J</creatorcontrib><creatorcontrib>Murthi, P</creatorcontrib><creatorcontrib>Borg, A</creatorcontrib><creatorcontrib>Kalionis, B</creatorcontrib><creatorcontrib>Moses, E.K</creatorcontrib><creatorcontrib>Brennecke, S.P</creatorcontrib><creatorcontrib>Keogh, R.J</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Placenta (Eastbourne)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Yong, H.E.J</au><au>Murthi, P</au><au>Borg, A</au><au>Kalionis, B</au><au>Moses, E.K</au><au>Brennecke, S.P</au><au>Keogh, R.J</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Increased decidual mRNA expression levels of candidate maternal pre-eclampsia susceptibility genes are associated with clinical severity</atitle><jtitle>Placenta (Eastbourne)</jtitle><addtitle>Placenta</addtitle><date>2014-02</date><risdate>2014</risdate><volume>35</volume><issue>2</issue><spage>117</spage><epage>124</epage><pages>117-124</pages><issn>0143-4004</issn><eissn>1532-3102</eissn><abstract>Abstract Introduction Pre-eclampsia (PE) has a familial association, with daughters of women who had PE during pregnancy having more than twice the risk of developing PE themselves. Through genome-wide linkage and genetic association studies in PE-affected families and large population samples, we previously identified the following as positional candidate maternal susceptibility genes for PE; ACVR1 , INHA , INHBB , ERAP1 , ERAP2 , LNPEP , COL4A1 and COL4A2 . The aims of this study were to determine mRNA expression levels of previously identified candidate maternal pre-eclampsia susceptibility genes from normotensive and severe PE (SPE) pregnancies and correlate mRNA expression levels with the clinical severity of SPE. Methods Third trimester decidual tissues were collected from both normotensive ( n  = 21) and SPE pregnancies ( n  = 24) and mRNA expression levels were determined by real-time PCR. Gene expression was then correlated with several parameters of clinical severity in SPE. Statistical significance was determined by Mann–Whitney U test and Spearman's Correlation. Results The data demonstrate significantly increased decidual mRNA expression levels of ACVR1 , INHBB , ERAP1 , ERAP2 , LNPEP , COL4A1 and COL4A2 in SPE ( p  &lt; 0.05). Increased mRNA expression levels of several genes – INHA , INHBB , COL4A1 and COL4A2 were correlated with earlier onset of PE and earlier delivery of the fetus ( p  &lt; 0.05). Conclusion These results suggest altered expression of maternal susceptibility genes may play roles in PE development and the course of disease severity.</abstract><cop>Netherlands</cop><pub>Elsevier Ltd</pub><pmid>24331737</pmid><doi>10.1016/j.placenta.2013.11.008</doi><tpages>8</tpages><orcidid>https://orcid.org/0000-0002-8814-752X</orcidid><orcidid>https://orcid.org/0000-0002-4025-5257</orcidid><oa>free_for_read</oa></addata></record>
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subjects Activin Receptors, Type I - biosynthesis
Adult
Clinical severity
Collagen Type IV - biosynthesis
Decidua
Decidua - metabolism
Female
Gene expression
Genetic Predisposition to Disease - genetics
Humans
Inhibin-beta Subunits - biosynthesis
Inhibins - biosynthesis
Internal Medicine
Obstetrics and Gynecology
Pre-eclampsia
Pre-Eclampsia - genetics
Pre-Eclampsia - metabolism
Pregnancy
Pregnancy Trimester, Third
RNA, Messenger - metabolism
Susceptibility genes
title Increased decidual mRNA expression levels of candidate maternal pre-eclampsia susceptibility genes are associated with clinical severity
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