Association of cord blood methylation fractions at imprinted insulin-like growth factor 2 (IGF2), plasma IGF2, and birth weight
Purpose: Altered methylation at Insulin-like Growth Factor 2 (IGF2) regulatory regions has previously been associated with obesity, and several malignancies including colon, esophageal, and prostate adenocarcinomas, presumably via changes in expression and/or loss of imprinting, but the functional s...
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| Veröffentlicht in: | Cancer causes & control 2012-04, Vol.23 (4), p.635-645 |
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| creator | Hoyo, Cathrine Fortner, Kimberly Murtha, Amy P. Schildkraut, Joellen M. Soubry, Adelheid Demark-Wahnefried, Wendy Jirtle, Randy L. Kurtzberg, Joanne Forman, Michele R. Overcash, Francine Huang, Zhiqing Murphy, Susan K. |
| description | Purpose: Altered methylation at Insulin-like Growth Factor 2 (IGF2) regulatory regions has previously been associated with obesity, and several malignancies including colon, esophageal, and prostate adenocarcinomas, presumably via changes in expression and/or loss of imprinting, but the functional significance of these DNA methylation marks have not been demonstrated in humans. We examined associations among DNA methylation at IGF2 differentially methylated regions (DMRs), circulating IGF2 protein concentrations in umbilical cord blood (UCB) and birth weight in newborns. Methods: Questionnaire data were obtained from 300 pregnant women recruited between 2005 and 2009. UCB DNA methylation was measured by bisulfite pyrosequencing. UCB plasma concentrations of soluble IGF2 were measured by ELISA assays. Generalized linear regression models were used to examine the relationship between DMR methylation and IGF2 levels. Results: Lower IGF2 DMR methylation was associated with elevated plasma IGF2 protein concentrations (ß = — 9.87, p < 0.01); an association that was stronger in infants born to obese women (pre-pregnancy BMI > 30 kg/m 2 , ß = -20.21, p < 0.0001). Elevated IGF2 concentrations were associated with higher birth weight (p < 0.0001) after adjusting for maternal race/ethnicity, pre-pregnancy BMI, cigarette smoking, gestational diabetes, and infant sex. These patterns of association were not apparent at the H19 DMR. Conclusion: Our data suggest that variation in 1GF2 DMR methylation is an important mechanism by which circulating IGF2 concentrations, a putative risk factor for obesity and cancers of the colon, esophagus, and prostate, are modulated; associations that may depend on pre-pregnancy obesity. |
| doi_str_mv | 10.1007/s10552-012-9932-y |
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We examined associations among DNA methylation at IGF2 differentially methylated regions (DMRs), circulating IGF2 protein concentrations in umbilical cord blood (UCB) and birth weight in newborns. Methods: Questionnaire data were obtained from 300 pregnant women recruited between 2005 and 2009. UCB DNA methylation was measured by bisulfite pyrosequencing. UCB plasma concentrations of soluble IGF2 were measured by ELISA assays. Generalized linear regression models were used to examine the relationship between DMR methylation and IGF2 levels. Results: Lower IGF2 DMR methylation was associated with elevated plasma IGF2 protein concentrations (ß = — 9.87, p < 0.01); an association that was stronger in infants born to obese women (pre-pregnancy BMI > 30 kg/m 2 , ß = -20.21, p < 0.0001). Elevated IGF2 concentrations were associated with higher birth weight (p < 0.0001) after adjusting for maternal race/ethnicity, pre-pregnancy BMI, cigarette smoking, gestational diabetes, and infant sex. These patterns of association were not apparent at the H19 DMR. Conclusion: Our data suggest that variation in 1GF2 DMR methylation is an important mechanism by which circulating IGF2 concentrations, a putative risk factor for obesity and cancers of the colon, esophagus, and prostate, are modulated; associations that may depend on pre-pregnancy obesity.</description><identifier>ISSN: 0957-5243</identifier><identifier>EISSN: 1573-7225</identifier><identifier>DOI: 10.1007/s10552-012-9932-y</identifier><identifier>PMID: 22392079</identifier><identifier>CODEN: CCCNEN</identifier><language>eng</language><publisher>Dordrecht: Springer</publisher><subject>Adenocarcinoma ; Biomedical and Life Sciences ; Biomedicine ; Birth weight ; Birth Weight - genetics ; Bisulfite ; body mass ; Body mass index ; Cancer ; Cancer Research ; Cigarette smoking ; Cigarettes ; Colon ; Colon cancer ; Cord blood ; Data processing ; Diabetes mellitus ; DNA ; DNA methylation ; DNA Methylation - genetics ; Enzyme-Linked Immunosorbent Assay ; Epidemiology ; Epigenetics ; Esophagus ; Ethnic groups ; Female ; Fetal Blood ; Genes ; Genomic Imprinting ; growth factors ; Gynecology ; Hematology ; Humans ; Imprinting ; Infant, Newborn ; Infants ; Insulin ; Insulin-like growth factor II ; Insulin-Like Growth Factor II - analysis ; Insulin-Like Growth Factor II - genetics ; Insulin-like growth factors ; Inventories ; Leukocytes ; Male ; Malignancy ; Methylation ; Obesity ; Obstetrics ; Oncology ; Original Paper ; Ovaries ; P values ; Plasma ; Pregnancy ; Prostate ; Proteins ; Public Health ; Races ; Regression analysis ; Regulatory sequences ; Risk factors ; Sex ; Umbilical cord ; Weight gain</subject><ispartof>Cancer causes & control, 2012-04, Vol.23 (4), p.635-645</ispartof><rights>The Author(s) 2012</rights><rights>Springer Science+Business Media B.V. 2012</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c589t-ac52f103ba233e510a01c5cd2af50f6613476d02458d5d3cdc10536e443f5f53</citedby><cites>FETCH-LOGICAL-c589t-ac52f103ba233e510a01c5cd2af50f6613476d02458d5d3cdc10536e443f5f53</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.jstor.org/stable/pdf/41472464$$EPDF$$P50$$Gjstor$$H</linktopdf><linktohtml>$$Uhttps://www.jstor.org/stable/41472464$$EHTML$$P50$$Gjstor$$H</linktohtml><link.rule.ids>230,314,780,784,803,885,27924,27925,41488,42557,51319,58017,58250</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/22392079$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Hoyo, Cathrine</creatorcontrib><creatorcontrib>Fortner, Kimberly</creatorcontrib><creatorcontrib>Murtha, Amy P.</creatorcontrib><creatorcontrib>Schildkraut, Joellen M.</creatorcontrib><creatorcontrib>Soubry, Adelheid</creatorcontrib><creatorcontrib>Demark-Wahnefried, Wendy</creatorcontrib><creatorcontrib>Jirtle, Randy L.</creatorcontrib><creatorcontrib>Kurtzberg, Joanne</creatorcontrib><creatorcontrib>Forman, Michele R.</creatorcontrib><creatorcontrib>Overcash, Francine</creatorcontrib><creatorcontrib>Huang, Zhiqing</creatorcontrib><creatorcontrib>Murphy, Susan K.</creatorcontrib><title>Association of cord blood methylation fractions at imprinted insulin-like growth factor 2 (IGF2), plasma IGF2, and birth weight</title><title>Cancer causes & control</title><addtitle>Cancer Causes Control</addtitle><addtitle>Cancer Causes Control</addtitle><description>Purpose: Altered methylation at Insulin-like Growth Factor 2 (IGF2) regulatory regions has previously been associated with obesity, and several malignancies including colon, esophageal, and prostate adenocarcinomas, presumably via changes in expression and/or loss of imprinting, but the functional significance of these DNA methylation marks have not been demonstrated in humans. We examined associations among DNA methylation at IGF2 differentially methylated regions (DMRs), circulating IGF2 protein concentrations in umbilical cord blood (UCB) and birth weight in newborns. Methods: Questionnaire data were obtained from 300 pregnant women recruited between 2005 and 2009. UCB DNA methylation was measured by bisulfite pyrosequencing. UCB plasma concentrations of soluble IGF2 were measured by ELISA assays. Generalized linear regression models were used to examine the relationship between DMR methylation and IGF2 levels. Results: Lower IGF2 DMR methylation was associated with elevated plasma IGF2 protein concentrations (ß = — 9.87, p < 0.01); an association that was stronger in infants born to obese women (pre-pregnancy BMI > 30 kg/m 2 , ß = -20.21, p < 0.0001). Elevated IGF2 concentrations were associated with higher birth weight (p < 0.0001) after adjusting for maternal race/ethnicity, pre-pregnancy BMI, cigarette smoking, gestational diabetes, and infant sex. These patterns of association were not apparent at the H19 DMR. Conclusion: Our data suggest that variation in 1GF2 DMR methylation is an important mechanism by which circulating IGF2 concentrations, a putative risk factor for obesity and cancers of the colon, esophagus, and prostate, are modulated; associations that may depend on pre-pregnancy obesity.</description><subject>Adenocarcinoma</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedicine</subject><subject>Birth weight</subject><subject>Birth Weight - genetics</subject><subject>Bisulfite</subject><subject>body mass</subject><subject>Body mass index</subject><subject>Cancer</subject><subject>Cancer Research</subject><subject>Cigarette smoking</subject><subject>Cigarettes</subject><subject>Colon</subject><subject>Colon cancer</subject><subject>Cord blood</subject><subject>Data processing</subject><subject>Diabetes mellitus</subject><subject>DNA</subject><subject>DNA methylation</subject><subject>DNA Methylation - genetics</subject><subject>Enzyme-Linked Immunosorbent Assay</subject><subject>Epidemiology</subject><subject>Epigenetics</subject><subject>Esophagus</subject><subject>Ethnic groups</subject><subject>Female</subject><subject>Fetal Blood</subject><subject>Genes</subject><subject>Genomic Imprinting</subject><subject>growth factors</subject><subject>Gynecology</subject><subject>Hematology</subject><subject>Humans</subject><subject>Imprinting</subject><subject>Infant, Newborn</subject><subject>Infants</subject><subject>Insulin</subject><subject>Insulin-like growth factor II</subject><subject>Insulin-Like Growth Factor II - analysis</subject><subject>Insulin-Like Growth Factor II - genetics</subject><subject>Insulin-like growth factors</subject><subject>Inventories</subject><subject>Leukocytes</subject><subject>Male</subject><subject>Malignancy</subject><subject>Methylation</subject><subject>Obesity</subject><subject>Obstetrics</subject><subject>Oncology</subject><subject>Original Paper</subject><subject>Ovaries</subject><subject>P values</subject><subject>Plasma</subject><subject>Pregnancy</subject><subject>Prostate</subject><subject>Proteins</subject><subject>Public Health</subject><subject>Races</subject><subject>Regression analysis</subject><subject>Regulatory sequences</subject><subject>Risk factors</subject><subject>Sex</subject><subject>Umbilical cord</subject><subject>Weight gain</subject><issn>0957-5243</issn><issn>1573-7225</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2012</creationdate><recordtype>article</recordtype><sourceid>C6C</sourceid><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><recordid>eNp9kk1v1DAQhi0EotvCD-AAsri0SA2Mx3ayviBVFS2VKnHp3fI6zq6XJF7spNWe-Os4Slk-Dj3Z1jzzjmfeIeQNg48MoPqUGEiJBTAslOJY7J-RBZMVLypE-ZwsQMmqkCj4ETlOaQsAskR4SY4QuUKo1IL8vEgpWG8GH3oaGmpDrOmqDaGmnRs2-3aONNHY6ZKoGajvdtH3g6up79PY-r5o_XdH1zE8DBvaZDJEivTs5voKP5zTXWtSZ-j0Oqemz_I-Zu7B-fVmeEVeNKZN7vXjeULurr7cXX4tbr9d31xe3BZWLtVQGCuxYcBXBjl3koEBZqWt0TQSmrJkXFRlDSjkspY1t7XNo-GlE4I3spH8hHyeZXfjqnO1df0QTatzH52Jex2M1_9Ger_R63CvOWccBGSB00eBGH6MLg2688m6tjW9C2PSSnJkSoHI5NmTZHZuueQlViqj7_9Dt2GMfZ6DVgKUyMXLDLEZsjGkFF1z-DWDSazS8xrovAZ6WgO9zznv_m73kPHb9wzgDKTJyrWLfyo_pfp2Ttqm7PBBVDBRoSgF_wXWeMdo</recordid><startdate>20120401</startdate><enddate>20120401</enddate><creator>Hoyo, Cathrine</creator><creator>Fortner, Kimberly</creator><creator>Murtha, Amy P.</creator><creator>Schildkraut, Joellen M.</creator><creator>Soubry, Adelheid</creator><creator>Demark-Wahnefried, Wendy</creator><creator>Jirtle, Randy L.</creator><creator>Kurtzberg, Joanne</creator><creator>Forman, Michele R.</creator><creator>Overcash, Francine</creator><creator>Huang, Zhiqing</creator><creator>Murphy, Susan K.</creator><general>Springer</general><general>Springer Netherlands</general><general>Springer Nature B.V</general><scope>C6C</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>7RV</scope><scope>7TO</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>H94</scope><scope>K9.</scope><scope>KB0</scope><scope>M0S</scope><scope>M1P</scope><scope>NAPCQ</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>7T2</scope><scope>7TM</scope><scope>7U1</scope><scope>7U2</scope><scope>C1K</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20120401</creationdate><title>Association of cord blood methylation fractions at imprinted insulin-like growth factor 2 (IGF2), plasma IGF2, and birth weight</title><author>Hoyo, Cathrine ; Fortner, Kimberly ; Murtha, Amy P. ; Schildkraut, Joellen M. ; Soubry, Adelheid ; Demark-Wahnefried, Wendy ; Jirtle, Randy L. ; Kurtzberg, Joanne ; Forman, Michele R. ; Overcash, Francine ; Huang, Zhiqing ; Murphy, Susan K.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c589t-ac52f103ba233e510a01c5cd2af50f6613476d02458d5d3cdc10536e443f5f53</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2012</creationdate><topic>Adenocarcinoma</topic><topic>Biomedical and Life Sciences</topic><topic>Biomedicine</topic><topic>Birth weight</topic><topic>Birth Weight - genetics</topic><topic>Bisulfite</topic><topic>body mass</topic><topic>Body mass index</topic><topic>Cancer</topic><topic>Cancer Research</topic><topic>Cigarette smoking</topic><topic>Cigarettes</topic><topic>Colon</topic><topic>Colon cancer</topic><topic>Cord blood</topic><topic>Data processing</topic><topic>Diabetes mellitus</topic><topic>DNA</topic><topic>DNA methylation</topic><topic>DNA Methylation - genetics</topic><topic>Enzyme-Linked Immunosorbent Assay</topic><topic>Epidemiology</topic><topic>Epigenetics</topic><topic>Esophagus</topic><topic>Ethnic groups</topic><topic>Female</topic><topic>Fetal Blood</topic><topic>Genes</topic><topic>Genomic Imprinting</topic><topic>growth factors</topic><topic>Gynecology</topic><topic>Hematology</topic><topic>Humans</topic><topic>Imprinting</topic><topic>Infant, Newborn</topic><topic>Infants</topic><topic>Insulin</topic><topic>Insulin-like growth factor II</topic><topic>Insulin-Like Growth Factor II - analysis</topic><topic>Insulin-Like Growth Factor II - genetics</topic><topic>Insulin-like growth factors</topic><topic>Inventories</topic><topic>Leukocytes</topic><topic>Male</topic><topic>Malignancy</topic><topic>Methylation</topic><topic>Obesity</topic><topic>Obstetrics</topic><topic>Oncology</topic><topic>Original Paper</topic><topic>Ovaries</topic><topic>P values</topic><topic>Plasma</topic><topic>Pregnancy</topic><topic>Prostate</topic><topic>Proteins</topic><topic>Public Health</topic><topic>Races</topic><topic>Regression analysis</topic><topic>Regulatory sequences</topic><topic>Risk factors</topic><topic>Sex</topic><topic>Umbilical cord</topic><topic>Weight gain</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Hoyo, Cathrine</creatorcontrib><creatorcontrib>Fortner, Kimberly</creatorcontrib><creatorcontrib>Murtha, Amy P.</creatorcontrib><creatorcontrib>Schildkraut, Joellen M.</creatorcontrib><creatorcontrib>Soubry, Adelheid</creatorcontrib><creatorcontrib>Demark-Wahnefried, Wendy</creatorcontrib><creatorcontrib>Jirtle, Randy L.</creatorcontrib><creatorcontrib>Kurtzberg, Joanne</creatorcontrib><creatorcontrib>Forman, Michele R.</creatorcontrib><creatorcontrib>Overcash, Francine</creatorcontrib><creatorcontrib>Huang, Zhiqing</creatorcontrib><creatorcontrib>Murphy, Susan K.</creatorcontrib><collection>Springer Nature OA Free Journals</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Nursing & Allied Health Database</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni)</collection><collection>ProQuest Central</collection><collection>ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Nursing & Allied Health Premium</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>Health and Safety Science Abstracts (Full archive)</collection><collection>Nucleic Acids Abstracts</collection><collection>Risk Abstracts</collection><collection>Safety Science and Risk</collection><collection>Environmental Sciences and Pollution Management</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Cancer causes & control</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Hoyo, Cathrine</au><au>Fortner, Kimberly</au><au>Murtha, Amy P.</au><au>Schildkraut, Joellen M.</au><au>Soubry, Adelheid</au><au>Demark-Wahnefried, Wendy</au><au>Jirtle, Randy L.</au><au>Kurtzberg, Joanne</au><au>Forman, Michele R.</au><au>Overcash, Francine</au><au>Huang, Zhiqing</au><au>Murphy, Susan K.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Association of cord blood methylation fractions at imprinted insulin-like growth factor 2 (IGF2), plasma IGF2, and birth weight</atitle><jtitle>Cancer causes & control</jtitle><stitle>Cancer Causes Control</stitle><addtitle>Cancer Causes Control</addtitle><date>2012-04-01</date><risdate>2012</risdate><volume>23</volume><issue>4</issue><spage>635</spage><epage>645</epage><pages>635-645</pages><issn>0957-5243</issn><eissn>1573-7225</eissn><coden>CCCNEN</coden><abstract>Purpose: Altered methylation at Insulin-like Growth Factor 2 (IGF2) regulatory regions has previously been associated with obesity, and several malignancies including colon, esophageal, and prostate adenocarcinomas, presumably via changes in expression and/or loss of imprinting, but the functional significance of these DNA methylation marks have not been demonstrated in humans. We examined associations among DNA methylation at IGF2 differentially methylated regions (DMRs), circulating IGF2 protein concentrations in umbilical cord blood (UCB) and birth weight in newborns. Methods: Questionnaire data were obtained from 300 pregnant women recruited between 2005 and 2009. UCB DNA methylation was measured by bisulfite pyrosequencing. UCB plasma concentrations of soluble IGF2 were measured by ELISA assays. Generalized linear regression models were used to examine the relationship between DMR methylation and IGF2 levels. Results: Lower IGF2 DMR methylation was associated with elevated plasma IGF2 protein concentrations (ß = — 9.87, p < 0.01); an association that was stronger in infants born to obese women (pre-pregnancy BMI > 30 kg/m 2 , ß = -20.21, p < 0.0001). Elevated IGF2 concentrations were associated with higher birth weight (p < 0.0001) after adjusting for maternal race/ethnicity, pre-pregnancy BMI, cigarette smoking, gestational diabetes, and infant sex. These patterns of association were not apparent at the H19 DMR. Conclusion: Our data suggest that variation in 1GF2 DMR methylation is an important mechanism by which circulating IGF2 concentrations, a putative risk factor for obesity and cancers of the colon, esophagus, and prostate, are modulated; associations that may depend on pre-pregnancy obesity.</abstract><cop>Dordrecht</cop><pub>Springer</pub><pmid>22392079</pmid><doi>10.1007/s10552-012-9932-y</doi><tpages>11</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Adenocarcinoma Biomedical and Life Sciences Biomedicine Birth weight Birth Weight - genetics Bisulfite body mass Body mass index Cancer Cancer Research Cigarette smoking Cigarettes Colon Colon cancer Cord blood Data processing Diabetes mellitus DNA DNA methylation DNA Methylation - genetics Enzyme-Linked Immunosorbent Assay Epidemiology Epigenetics Esophagus Ethnic groups Female Fetal Blood Genes Genomic Imprinting growth factors Gynecology Hematology Humans Imprinting Infant, Newborn Infants Insulin Insulin-like growth factor II Insulin-Like Growth Factor II - analysis Insulin-Like Growth Factor II - genetics Insulin-like growth factors Inventories Leukocytes Male Malignancy Methylation Obesity Obstetrics Oncology Original Paper Ovaries P values Plasma Pregnancy Prostate Proteins Public Health Races Regression analysis Regulatory sequences Risk factors Sex Umbilical cord Weight gain |
| title | Association of cord blood methylation fractions at imprinted insulin-like growth factor 2 (IGF2), plasma IGF2, and birth weight |
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