Expression quantitative trait loci for ETV4 and MEOX1 are associated with adult asthma in Japanese populations
ETS variant transcription factor 4 (ETV4) is a recently identified transcription factor that regulates gene expression-based biomarkers of asthma and IL6 production in an airway epithelial cell line. Given that ETV4 has not yet been implicated in asthma genetics, we performed genetic association stu...
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| creator | Yatagai, Yohei Oshima, Hisayuki Sakamoto, Tohru Shigemasa, Rie Kitazawa, Haruna Hyodo, Kentaro Masuko, Hironori Iijima, Hiroaki Naito, Takashi Saito, Takefumi Hirota, Tomomitsu Tamari, Mayumi Hizawa, Nobuyuki |
| description | ETS variant transcription factor 4 (ETV4) is a recently identified transcription factor that regulates gene expression-based biomarkers of asthma and IL6 production in an airway epithelial cell line. Given that
ETV4
has not yet been implicated in asthma genetics, we performed genetic association studies of adult asthma in the
ETV4
region using two independent Japanese cohorts (a total of 1532 controls and 783 cases). SNPs located between
ETV4
and
mesenchyme homeobox 1
(
MEOX1
) were significantly associated with adult asthma, including rs4792901 and rs2880540 (
P
= 5.63E−5 and 2.77E−5, respectively). The CC haplotype of these two SNPs was also significantly associated with adult asthma (
P
= 8.43E−7). Even when both SNPs were included in a logistic regression model, the association of either rs4792901 or rs2880540 remained significant (
P
= 0.013 or 0.007, respectively), suggesting that the two SNPs may have independent effects on the development of asthma. Both SNPs were expression quantitative trait loci, and the asthma risk alleles at both SNPs were correlated with increased levels of
ETV4
mRNA expression. In addition, the asthma risk allele at rs4792901 was associated with increased serum IL6 levels (
P
= 0.041) in 651 healthy adults. Our findings imply that ETV4 is involved in the pathogenesis of asthma, possibly through the heightened production of IL6. |
| doi_str_mv | 10.1038/s41598-021-98348-3 |
| format | Article |
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ETV4
has not yet been implicated in asthma genetics, we performed genetic association studies of adult asthma in the
ETV4
region using two independent Japanese cohorts (a total of 1532 controls and 783 cases). SNPs located between
ETV4
and
mesenchyme homeobox 1
(
MEOX1
) were significantly associated with adult asthma, including rs4792901 and rs2880540 (
P
= 5.63E−5 and 2.77E−5, respectively). The CC haplotype of these two SNPs was also significantly associated with adult asthma (
P
= 8.43E−7). Even when both SNPs were included in a logistic regression model, the association of either rs4792901 or rs2880540 remained significant (
P
= 0.013 or 0.007, respectively), suggesting that the two SNPs may have independent effects on the development of asthma. Both SNPs were expression quantitative trait loci, and the asthma risk alleles at both SNPs were correlated with increased levels of
ETV4
mRNA expression. In addition, the asthma risk allele at rs4792901 was associated with increased serum IL6 levels (
P
= 0.041) in 651 healthy adults. Our findings imply that ETV4 is involved in the pathogenesis of asthma, possibly through the heightened production of IL6.</description><identifier>ISSN: 2045-2322</identifier><identifier>EISSN: 2045-2322</identifier><identifier>DOI: 10.1038/s41598-021-98348-3</identifier><identifier>PMID: 34552174</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>631/208 ; 631/250 ; 631/337 ; 692/308 ; 692/4017 ; 692/420 ; 692/499 ; Adult ; Aged ; Aged, 80 and over ; Alleles ; Asthma ; Asthma - genetics ; Case-Control Studies ; Epithelial cells ; ETS protein ; Female ; Gene expression ; Gene mapping ; Genetic Predisposition to Disease - genetics ; Genetics ; Haplotypes ; Health risks ; Homeobox ; Homeodomain Proteins - genetics ; Humanities and Social Sciences ; Humans ; Interleukin 6 ; Japan - epidemiology ; Male ; Mesenchyme ; Middle Aged ; multidisciplinary ; Multidisciplinary Sciences ; Polymorphism, Single Nucleotide - genetics ; Proto-Oncogene Proteins c-ets - genetics ; Quantitative trait loci ; Quantitative Trait Loci - genetics ; Science ; Science & Technology ; Science & Technology - Other Topics ; Science (multidisciplinary) ; Single-nucleotide polymorphism ; Transcription factors ; Transcription Factors - genetics ; Young Adult</subject><ispartof>Scientific reports, 2021-09, Vol.11 (1), p.18791-18791, Article 18791</ispartof><rights>The Author(s) 2021</rights><rights>2021. The Author(s).</rights><rights>The Author(s) 2021. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>true</woscitedreferencessubscribed><woscitedreferencescount>2</woscitedreferencescount><woscitedreferencesoriginalsourcerecordid>wos000700297100042</woscitedreferencesoriginalsourcerecordid><citedby>FETCH-LOGICAL-c540t-2abd127e570cd21c3903e6c1808e410e41bc7f5f65fc63a34b1d9ee99d34beed3</citedby><cites>FETCH-LOGICAL-c540t-2abd127e570cd21c3903e6c1808e410e41bc7f5f65fc63a34b1d9ee99d34beed3</cites><orcidid>0000-0002-8876-1466 ; 0000-0001-7234-1275</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8458279/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8458279/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,315,728,781,785,865,886,2103,2115,27928,27929,39262,41124,42193,51580,53795,53797</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/34552174$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Yatagai, Yohei</creatorcontrib><creatorcontrib>Oshima, Hisayuki</creatorcontrib><creatorcontrib>Sakamoto, Tohru</creatorcontrib><creatorcontrib>Shigemasa, Rie</creatorcontrib><creatorcontrib>Kitazawa, Haruna</creatorcontrib><creatorcontrib>Hyodo, Kentaro</creatorcontrib><creatorcontrib>Masuko, Hironori</creatorcontrib><creatorcontrib>Iijima, Hiroaki</creatorcontrib><creatorcontrib>Naito, Takashi</creatorcontrib><creatorcontrib>Saito, Takefumi</creatorcontrib><creatorcontrib>Hirota, Tomomitsu</creatorcontrib><creatorcontrib>Tamari, Mayumi</creatorcontrib><creatorcontrib>Hizawa, Nobuyuki</creatorcontrib><title>Expression quantitative trait loci for ETV4 and MEOX1 are associated with adult asthma in Japanese populations</title><title>Scientific reports</title><addtitle>Sci Rep</addtitle><addtitle>SCI REP-UK</addtitle><addtitle>Sci Rep</addtitle><description>ETS variant transcription factor 4 (ETV4) is a recently identified transcription factor that regulates gene expression-based biomarkers of asthma and IL6 production in an airway epithelial cell line. Given that
ETV4
has not yet been implicated in asthma genetics, we performed genetic association studies of adult asthma in the
ETV4
region using two independent Japanese cohorts (a total of 1532 controls and 783 cases). SNPs located between
ETV4
and
mesenchyme homeobox 1
(
MEOX1
) were significantly associated with adult asthma, including rs4792901 and rs2880540 (
P
= 5.63E−5 and 2.77E−5, respectively). The CC haplotype of these two SNPs was also significantly associated with adult asthma (
P
= 8.43E−7). Even when both SNPs were included in a logistic regression model, the association of either rs4792901 or rs2880540 remained significant (
P
= 0.013 or 0.007, respectively), suggesting that the two SNPs may have independent effects on the development of asthma. Both SNPs were expression quantitative trait loci, and the asthma risk alleles at both SNPs were correlated with increased levels of
ETV4
mRNA expression. In addition, the asthma risk allele at rs4792901 was associated with increased serum IL6 levels (
P
= 0.041) in 651 healthy adults. Our findings imply that ETV4 is involved in the pathogenesis of asthma, possibly through the heightened production of IL6.</description><subject>631/208</subject><subject>631/250</subject><subject>631/337</subject><subject>692/308</subject><subject>692/4017</subject><subject>692/420</subject><subject>692/499</subject><subject>Adult</subject><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>Alleles</subject><subject>Asthma</subject><subject>Asthma - genetics</subject><subject>Case-Control Studies</subject><subject>Epithelial cells</subject><subject>ETS protein</subject><subject>Female</subject><subject>Gene expression</subject><subject>Gene mapping</subject><subject>Genetic Predisposition to Disease - genetics</subject><subject>Genetics</subject><subject>Haplotypes</subject><subject>Health risks</subject><subject>Homeobox</subject><subject>Homeodomain Proteins - genetics</subject><subject>Humanities and Social Sciences</subject><subject>Humans</subject><subject>Interleukin 6</subject><subject>Japan - epidemiology</subject><subject>Male</subject><subject>Mesenchyme</subject><subject>Middle Aged</subject><subject>multidisciplinary</subject><subject>Multidisciplinary Sciences</subject><subject>Polymorphism, Single Nucleotide - genetics</subject><subject>Proto-Oncogene Proteins c-ets - genetics</subject><subject>Quantitative trait loci</subject><subject>Quantitative Trait Loci - genetics</subject><subject>Science</subject><subject>Science & Technology</subject><subject>Science & Technology - Other Topics</subject><subject>Science (multidisciplinary)</subject><subject>Single-nucleotide polymorphism</subject><subject>Transcription factors</subject><subject>Transcription Factors - genetics</subject><subject>Young Adult</subject><issn>2045-2322</issn><issn>2045-2322</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>C6C</sourceid><sourceid>HGBXW</sourceid><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>DOA</sourceid><recordid>eNqNkl1rFDEUhgdRbKn9A15IwBuhjOZzZ3IjyLJqpdKbKt6FTHJmN8tsMk0yrf57405dWy_EQMjhnOe8JCdvVT0n-DXBrH2TOBGyrTEltWwZb2v2qDqmmIuaMkof34uPqtOUtrgsQSUn8ml1xLgQlDT8uPKr72OElFzw6HrSPruss7sBlKN2GQ3BONSHiFZXXznS3qLPq8tvBOkISKdUqjqDRbcub5C205BLNm92GjmPPulRe0iAxjBOQ1ENPj2rnvR6SHB6d55UX96vrpYf64vLD-fLdxe1ERznmurOEtqAaLCxlBgmMYOFIS1ugRNcdmeaXvQL0ZsF04x3xEoAKW0JASw7qc5nXRv0Vo3R7XT8oYJ2ap8Ica10zM4MoBoqO5CA-14ILhedJgY6a3RjgXdtj4vW21lrnLodWAO-zGZ4IPqw4t1GrcONarloaSOLwKs7gRiuJ0hZ7VwyMAxlPGFKiopGtIxg3hT05V_oNkzRl1HtqfLlDNNC0ZkyMaQUoT9chmD1yx1qdocq7lB7dyhWml7cf8ah5bcXCtDOwC10oU_GgTdwwIp9GoypbEiJOF3ufRL8Mkw-l9az_28tNJvpVAi_hvjnkf-4_09Sk-ei</recordid><startdate>20210922</startdate><enddate>20210922</enddate><creator>Yatagai, Yohei</creator><creator>Oshima, Hisayuki</creator><creator>Sakamoto, Tohru</creator><creator>Shigemasa, Rie</creator><creator>Kitazawa, Haruna</creator><creator>Hyodo, Kentaro</creator><creator>Masuko, Hironori</creator><creator>Iijima, Hiroaki</creator><creator>Naito, Takashi</creator><creator>Saito, Takefumi</creator><creator>Hirota, Tomomitsu</creator><creator>Tamari, Mayumi</creator><creator>Hizawa, Nobuyuki</creator><general>Nature Publishing Group UK</general><general>NATURE PORTFOLIO</general><general>Nature Publishing Group</general><general>Nature Portfolio</general><scope>C6C</scope><scope>BLEPL</scope><scope>DTL</scope><scope>HGBXW</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>3V.</scope><scope>7X7</scope><scope>7XB</scope><scope>88A</scope><scope>88E</scope><scope>88I</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M2P</scope><scope>M7P</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>Q9U</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope><orcidid>https://orcid.org/0000-0002-8876-1466</orcidid><orcidid>https://orcid.org/0000-0001-7234-1275</orcidid></search><sort><creationdate>20210922</creationdate><title>Expression quantitative trait loci for ETV4 and MEOX1 are associated with adult asthma in Japanese populations</title><author>Yatagai, Yohei ; Oshima, Hisayuki ; Sakamoto, Tohru ; Shigemasa, Rie ; Kitazawa, Haruna ; Hyodo, Kentaro ; Masuko, Hironori ; Iijima, Hiroaki ; Naito, Takashi ; Saito, Takefumi ; Hirota, Tomomitsu ; Tamari, Mayumi ; Hizawa, Nobuyuki</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c540t-2abd127e570cd21c3903e6c1808e410e41bc7f5f65fc63a34b1d9ee99d34beed3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>631/208</topic><topic>631/250</topic><topic>631/337</topic><topic>692/308</topic><topic>692/4017</topic><topic>692/420</topic><topic>692/499</topic><topic>Adult</topic><topic>Aged</topic><topic>Aged, 80 and over</topic><topic>Alleles</topic><topic>Asthma</topic><topic>Asthma - genetics</topic><topic>Case-Control Studies</topic><topic>Epithelial cells</topic><topic>ETS protein</topic><topic>Female</topic><topic>Gene expression</topic><topic>Gene mapping</topic><topic>Genetic Predisposition to Disease - genetics</topic><topic>Genetics</topic><topic>Haplotypes</topic><topic>Health risks</topic><topic>Homeobox</topic><topic>Homeodomain Proteins - genetics</topic><topic>Humanities and Social Sciences</topic><topic>Humans</topic><topic>Interleukin 6</topic><topic>Japan - epidemiology</topic><topic>Male</topic><topic>Mesenchyme</topic><topic>Middle Aged</topic><topic>multidisciplinary</topic><topic>Multidisciplinary Sciences</topic><topic>Polymorphism, Single Nucleotide - genetics</topic><topic>Proto-Oncogene Proteins c-ets - genetics</topic><topic>Quantitative trait loci</topic><topic>Quantitative Trait Loci - genetics</topic><topic>Science</topic><topic>Science & Technology</topic><topic>Science & Technology - Other Topics</topic><topic>Science (multidisciplinary)</topic><topic>Single-nucleotide polymorphism</topic><topic>Transcription factors</topic><topic>Transcription Factors - 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Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>Scientific reports</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Yatagai, Yohei</au><au>Oshima, Hisayuki</au><au>Sakamoto, Tohru</au><au>Shigemasa, Rie</au><au>Kitazawa, Haruna</au><au>Hyodo, Kentaro</au><au>Masuko, Hironori</au><au>Iijima, Hiroaki</au><au>Naito, Takashi</au><au>Saito, Takefumi</au><au>Hirota, Tomomitsu</au><au>Tamari, Mayumi</au><au>Hizawa, Nobuyuki</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Expression quantitative trait loci for ETV4 and MEOX1 are associated with adult asthma in Japanese populations</atitle><jtitle>Scientific reports</jtitle><stitle>Sci Rep</stitle><stitle>SCI REP-UK</stitle><addtitle>Sci Rep</addtitle><date>2021-09-22</date><risdate>2021</risdate><volume>11</volume><issue>1</issue><spage>18791</spage><epage>18791</epage><pages>18791-18791</pages><artnum>18791</artnum><issn>2045-2322</issn><eissn>2045-2322</eissn><abstract>ETS variant transcription factor 4 (ETV4) is a recently identified transcription factor that regulates gene expression-based biomarkers of asthma and IL6 production in an airway epithelial cell line. Given that
ETV4
has not yet been implicated in asthma genetics, we performed genetic association studies of adult asthma in the
ETV4
region using two independent Japanese cohorts (a total of 1532 controls and 783 cases). SNPs located between
ETV4
and
mesenchyme homeobox 1
(
MEOX1
) were significantly associated with adult asthma, including rs4792901 and rs2880540 (
P
= 5.63E−5 and 2.77E−5, respectively). The CC haplotype of these two SNPs was also significantly associated with adult asthma (
P
= 8.43E−7). Even when both SNPs were included in a logistic regression model, the association of either rs4792901 or rs2880540 remained significant (
P
= 0.013 or 0.007, respectively), suggesting that the two SNPs may have independent effects on the development of asthma. Both SNPs were expression quantitative trait loci, and the asthma risk alleles at both SNPs were correlated with increased levels of
ETV4
mRNA expression. In addition, the asthma risk allele at rs4792901 was associated with increased serum IL6 levels (
P
= 0.041) in 651 healthy adults. Our findings imply that ETV4 is involved in the pathogenesis of asthma, possibly through the heightened production of IL6.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>34552174</pmid><doi>10.1038/s41598-021-98348-3</doi><tpages>9</tpages><orcidid>https://orcid.org/0000-0002-8876-1466</orcidid><orcidid>https://orcid.org/0000-0001-7234-1275</orcidid><oa>free_for_read</oa></addata></record> |
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| source | MEDLINE; DOAJ Directory of Open Access Journals; Springer Nature OA Free Journals; Nature Free; Web of Science - Science Citation Index Expanded - 2021<img src="https://exlibris-pub.s3.amazonaws.com/fromwos-v2.jpg" />; EZB-FREE-00999 freely available EZB journals; PubMed Central; Free Full-Text Journals in Chemistry |
| subjects | 631/208 631/250 631/337 692/308 692/4017 692/420 692/499 Adult Aged Aged, 80 and over Alleles Asthma Asthma - genetics Case-Control Studies Epithelial cells ETS protein Female Gene expression Gene mapping Genetic Predisposition to Disease - genetics Genetics Haplotypes Health risks Homeobox Homeodomain Proteins - genetics Humanities and Social Sciences Humans Interleukin 6 Japan - epidemiology Male Mesenchyme Middle Aged multidisciplinary Multidisciplinary Sciences Polymorphism, Single Nucleotide - genetics Proto-Oncogene Proteins c-ets - genetics Quantitative trait loci Quantitative Trait Loci - genetics Science Science & Technology Science & Technology - Other Topics Science (multidisciplinary) Single-nucleotide polymorphism Transcription factors Transcription Factors - genetics Young Adult |
| title | Expression quantitative trait loci for ETV4 and MEOX1 are associated with adult asthma in Japanese populations |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-16T13%3A37%3A48IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Expression%20quantitative%20trait%20loci%20for%20ETV4%20and%20MEOX1%20are%20associated%20with%20adult%20asthma%20in%20Japanese%20populations&rft.jtitle=Scientific%20reports&rft.au=Yatagai,%20Yohei&rft.date=2021-09-22&rft.volume=11&rft.issue=1&rft.spage=18791&rft.epage=18791&rft.pages=18791-18791&rft.artnum=18791&rft.issn=2045-2322&rft.eissn=2045-2322&rft_id=info:doi/10.1038/s41598-021-98348-3&rft_dat=%3Cproquest_pubme%3E2575831047%3C/proquest_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2575159302&rft_id=info:pmid/34552174&rft_doaj_id=oai_doaj_org_article_729be9e0ff55496ba1cebdca7de4b8f0&rfr_iscdi=true |