Genetic Contribution of Variants near SORT1 and APOE on LDL Cholesterol Independent of Obesity in Children
To assess potential effects of variants in six lipid modulating genes (SORT1, HMGCR, MLXIPL, FADS2, APOE and MAFB) on early development of dyslipidemia independent of the degree of obesity in children, we investigated their association with total (TC), low density lipoprotein (LDL-C), high density l...
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| creator | Breitling, Clara Gross, Arnd Büttner, Petra Weise, Sebastian Schleinitz, Dorit Kiess, Wieland Scholz, Markus Kovacs, Peter Körner, Antje |
| description | To assess potential effects of variants in six lipid modulating genes (SORT1, HMGCR, MLXIPL, FADS2, APOE and MAFB) on early development of dyslipidemia independent of the degree of obesity in children, we investigated their association with total (TC), low density lipoprotein (LDL-C), high density lipoprotein (HDL-C) cholesterol and triglyceride (TG) levels in 594 children. Furthermore, we evaluated the expression profile of the candidate genes during human adipocyte differentiation.
Expression of selected genes increased 10(1) to >10(4) fold during human adipocyte differentiation, suggesting a potential link with adipogenesis. In genetic association studies adjusted for age, BMI SDS and sex, we identified significant associations for rs599839 near SORT1 with TC and LDL-C and for rs4420638 near APOE with TC and LDL-C. We performed Bayesian modelling of the combined lipid phenotype of HDL-C, LDL-C and TG to identify potentially causal polygenic effects on this multi-dimensional phenotype and considering obesity, age and sex as a-priori modulating factors. This analysis confirmed that rs599839 and rs4420638 affect LDL-C.
We show that lipid modulating genes are dynamically regulated during adipogenesis and that variants near SORT1 and APOE influence lipid levels independent of obesity in children. Bayesian modelling suggests causal effects of these variants. |
| doi_str_mv | 10.1371/journal.pone.0138064 |
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Expression of selected genes increased 10(1) to >10(4) fold during human adipocyte differentiation, suggesting a potential link with adipogenesis. In genetic association studies adjusted for age, BMI SDS and sex, we identified significant associations for rs599839 near SORT1 with TC and LDL-C and for rs4420638 near APOE with TC and LDL-C. We performed Bayesian modelling of the combined lipid phenotype of HDL-C, LDL-C and TG to identify potentially causal polygenic effects on this multi-dimensional phenotype and considering obesity, age and sex as a-priori modulating factors. This analysis confirmed that rs599839 and rs4420638 affect LDL-C.
We show that lipid modulating genes are dynamically regulated during adipogenesis and that variants near SORT1 and APOE influence lipid levels independent of obesity in children. Bayesian modelling suggests causal effects of these variants.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0138064</identifier><identifier>PMID: 26375028</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Adaptor Proteins, Vesicular Transport - genetics ; Adipogenesis ; Adults ; Apolipoprotein E ; Apolipoproteins E - genetics ; Bayes Theorem ; Bayesian analysis ; Body mass ; Cardiovascular disease ; Care and treatment ; Child ; Childhood obesity ; Children ; Children & youth ; Childrens health ; Cholesterol ; Cholesterol, LDL - blood ; Development and progression ; Differentiation ; Dyslipidemia ; Dyslipidemias - blood ; Dyslipidemias - etiology ; Dyslipidemias - pathology ; Epidemiology ; Fatty acids ; Female ; Gene expression ; Gene loci ; Genes ; Genetic aspects ; Genetic Predisposition to Disease ; Genomics ; Health informatics ; High density lipoprotein ; Hospitals ; Humans ; Laboratories ; Life assessment ; Lipids ; Low density lipoprotein ; Low density lipoproteins ; Male ; Metabolism ; Modelling ; Obesity ; Obesity - blood ; Obesity - complications ; Obesity - pathology ; Pediatrics ; Phenotypes ; Polymerase Chain Reaction ; Polymorphism, Single Nucleotide - genetics ; Sex ; Studies ; Systematic review ; Teenagers ; Triglycerides ; Womens health</subject><ispartof>PloS one, 2015-09, Vol.10 (9), p.e0138064-e0138064</ispartof><rights>COPYRIGHT 2015 Public Library of Science</rights><rights>2015 Breitling et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2015 Breitling et al 2015 Breitling et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c692t-eef9aed8a5beddb8a752270cfd10006c1eeb62b91848db838edb3952ec2f59793</citedby><cites>FETCH-LOGICAL-c692t-eef9aed8a5beddb8a752270cfd10006c1eeb62b91848db838edb3952ec2f59793</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4573320/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4573320/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,864,885,2102,2928,23866,27924,27925,53791,53793,79600,79601</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/26375028$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Böttcher, Yvonne</contributor><creatorcontrib>Breitling, Clara</creatorcontrib><creatorcontrib>Gross, Arnd</creatorcontrib><creatorcontrib>Büttner, Petra</creatorcontrib><creatorcontrib>Weise, Sebastian</creatorcontrib><creatorcontrib>Schleinitz, Dorit</creatorcontrib><creatorcontrib>Kiess, Wieland</creatorcontrib><creatorcontrib>Scholz, Markus</creatorcontrib><creatorcontrib>Kovacs, Peter</creatorcontrib><creatorcontrib>Körner, Antje</creatorcontrib><title>Genetic Contribution of Variants near SORT1 and APOE on LDL Cholesterol Independent of Obesity in Children</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>To assess potential effects of variants in six lipid modulating genes (SORT1, HMGCR, MLXIPL, FADS2, APOE and MAFB) on early development of dyslipidemia independent of the degree of obesity in children, we investigated their association with total (TC), low density lipoprotein (LDL-C), high density lipoprotein (HDL-C) cholesterol and triglyceride (TG) levels in 594 children. Furthermore, we evaluated the expression profile of the candidate genes during human adipocyte differentiation.
Expression of selected genes increased 10(1) to >10(4) fold during human adipocyte differentiation, suggesting a potential link with adipogenesis. In genetic association studies adjusted for age, BMI SDS and sex, we identified significant associations for rs599839 near SORT1 with TC and LDL-C and for rs4420638 near APOE with TC and LDL-C. We performed Bayesian modelling of the combined lipid phenotype of HDL-C, LDL-C and TG to identify potentially causal polygenic effects on this multi-dimensional phenotype and considering obesity, age and sex as a-priori modulating factors. This analysis confirmed that rs599839 and rs4420638 affect LDL-C.
We show that lipid modulating genes are dynamically regulated during adipogenesis and that variants near SORT1 and APOE influence lipid levels independent of obesity in children. Bayesian modelling suggests causal effects of these variants.</description><subject>Adaptor Proteins, Vesicular Transport - genetics</subject><subject>Adipogenesis</subject><subject>Adults</subject><subject>Apolipoprotein E</subject><subject>Apolipoproteins E - genetics</subject><subject>Bayes Theorem</subject><subject>Bayesian analysis</subject><subject>Body mass</subject><subject>Cardiovascular disease</subject><subject>Care and treatment</subject><subject>Child</subject><subject>Childhood obesity</subject><subject>Children</subject><subject>Children & youth</subject><subject>Childrens health</subject><subject>Cholesterol</subject><subject>Cholesterol, LDL - blood</subject><subject>Development and progression</subject><subject>Differentiation</subject><subject>Dyslipidemia</subject><subject>Dyslipidemias - blood</subject><subject>Dyslipidemias - etiology</subject><subject>Dyslipidemias - pathology</subject><subject>Epidemiology</subject><subject>Fatty acids</subject><subject>Female</subject><subject>Gene expression</subject><subject>Gene loci</subject><subject>Genes</subject><subject>Genetic aspects</subject><subject>Genetic Predisposition to Disease</subject><subject>Genomics</subject><subject>Health informatics</subject><subject>High density lipoprotein</subject><subject>Hospitals</subject><subject>Humans</subject><subject>Laboratories</subject><subject>Life assessment</subject><subject>Lipids</subject><subject>Low density lipoprotein</subject><subject>Low density lipoproteins</subject><subject>Male</subject><subject>Metabolism</subject><subject>Modelling</subject><subject>Obesity</subject><subject>Obesity - blood</subject><subject>Obesity - complications</subject><subject>Obesity - pathology</subject><subject>Pediatrics</subject><subject>Phenotypes</subject><subject>Polymerase Chain Reaction</subject><subject>Polymorphism, Single Nucleotide - genetics</subject><subject>Sex</subject><subject>Studies</subject><subject>Systematic review</subject><subject>Teenagers</subject><subject>Triglycerides</subject><subject>Womens health</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><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>eNqNk19v0zAUxSMEYqPwDRBEQkLw0OI_ceK8IFVljEqViraxV8txblpXrt3ZCWLfHrfNpgbtAUVKIvt3jn2PfZPkLUYTTAv8ZeM6b6WZ7JyFCcKUozx7lpzjkpJxThB9fvJ_lrwKYYMQozzPXyZnJKcFQ4SfJ5tLsNBqlc6cbb2uulY7m7omvZVeS9uG1IL06fXy6gan0tbp9OfyIo3I4tsina2dgdCCdyad2xp2EF-23cuXFQTd3qfaRkqb2oN9nbxopAnwpv-Okl_fL25mP8aL5eV8Nl2MVV6SdgzQlBJqLlkFdV1xWTBCCqSaGiOEcoUBqpxUJeYZj9OUQ13RkhFQpGFlUdJR8v7ouzMuiD6mIHCBS8IZ4TgS8yNRO7kRO6-30t8LJ7U4DDi_EtLHUAwIpViGG14ohnCGFK2w4iBxWTWsQKTk0etrv1pXbaFWsX4vzcB0OGP1Wqzcb5GxgtJ4NqPkU2_g3V0X4xRbHRQYIy247rBvWmY0IyyiH_5Bn66up1YyFqBt4-K6am8qphnhnGYY7_c9eYKKTw1breKdanQcHwg-DwSRaeFPu5JdCGJ-ffX_7PJ2yH48YdcgTbsOzhwuYhiC2RFU3oXgoXkMGSOxb4mHNMS-JUTfElH27vSAHkUPPUD_Ah5tBWc</recordid><startdate>20150916</startdate><enddate>20150916</enddate><creator>Breitling, Clara</creator><creator>Gross, Arnd</creator><creator>Büttner, Petra</creator><creator>Weise, Sebastian</creator><creator>Schleinitz, Dorit</creator><creator>Kiess, Wieland</creator><creator>Scholz, Markus</creator><creator>Kovacs, Peter</creator><creator>Körner, Antje</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</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>IOV</scope><scope>ISR</scope><scope>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QO</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TG</scope><scope>7TM</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PDBOC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>20150916</creationdate><title>Genetic Contribution of Variants near SORT1 and APOE on LDL Cholesterol Independent of Obesity in Children</title><author>Breitling, Clara ; Gross, Arnd ; Büttner, Petra ; Weise, Sebastian ; Schleinitz, Dorit ; Kiess, Wieland ; Scholz, Markus ; Kovacs, Peter ; Körner, Antje</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c692t-eef9aed8a5beddb8a752270cfd10006c1eeb62b91848db838edb3952ec2f59793</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>Adaptor Proteins, Vesicular Transport - 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Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Breitling, Clara</au><au>Gross, Arnd</au><au>Büttner, Petra</au><au>Weise, Sebastian</au><au>Schleinitz, Dorit</au><au>Kiess, Wieland</au><au>Scholz, Markus</au><au>Kovacs, Peter</au><au>Körner, Antje</au><au>Böttcher, Yvonne</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Genetic Contribution of Variants near SORT1 and APOE on LDL Cholesterol Independent of Obesity in Children</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2015-09-16</date><risdate>2015</risdate><volume>10</volume><issue>9</issue><spage>e0138064</spage><epage>e0138064</epage><pages>e0138064-e0138064</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>To assess potential effects of variants in six lipid modulating genes (SORT1, HMGCR, MLXIPL, FADS2, APOE and MAFB) on early development of dyslipidemia independent of the degree of obesity in children, we investigated their association with total (TC), low density lipoprotein (LDL-C), high density lipoprotein (HDL-C) cholesterol and triglyceride (TG) levels in 594 children. Furthermore, we evaluated the expression profile of the candidate genes during human adipocyte differentiation.
Expression of selected genes increased 10(1) to >10(4) fold during human adipocyte differentiation, suggesting a potential link with adipogenesis. In genetic association studies adjusted for age, BMI SDS and sex, we identified significant associations for rs599839 near SORT1 with TC and LDL-C and for rs4420638 near APOE with TC and LDL-C. We performed Bayesian modelling of the combined lipid phenotype of HDL-C, LDL-C and TG to identify potentially causal polygenic effects on this multi-dimensional phenotype and considering obesity, age and sex as a-priori modulating factors. This analysis confirmed that rs599839 and rs4420638 affect LDL-C.
We show that lipid modulating genes are dynamically regulated during adipogenesis and that variants near SORT1 and APOE influence lipid levels independent of obesity in children. Bayesian modelling suggests causal effects of these variants.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>26375028</pmid><doi>10.1371/journal.pone.0138064</doi><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1932-6203 |
| ispartof | PloS one, 2015-09, Vol.10 (9), p.e0138064-e0138064 |
| issn | 1932-6203 1932-6203 |
| language | eng |
| recordid | cdi_plos_journals_1719285281 |
| source | MEDLINE; DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Public Library of Science (PLoS); PubMed Central; Free Full-Text Journals in Chemistry |
| subjects | Adaptor Proteins, Vesicular Transport - genetics Adipogenesis Adults Apolipoprotein E Apolipoproteins E - genetics Bayes Theorem Bayesian analysis Body mass Cardiovascular disease Care and treatment Child Childhood obesity Children Children & youth Childrens health Cholesterol Cholesterol, LDL - blood Development and progression Differentiation Dyslipidemia Dyslipidemias - blood Dyslipidemias - etiology Dyslipidemias - pathology Epidemiology Fatty acids Female Gene expression Gene loci Genes Genetic aspects Genetic Predisposition to Disease Genomics Health informatics High density lipoprotein Hospitals Humans Laboratories Life assessment Lipids Low density lipoprotein Low density lipoproteins Male Metabolism Modelling Obesity Obesity - blood Obesity - complications Obesity - pathology Pediatrics Phenotypes Polymerase Chain Reaction Polymorphism, Single Nucleotide - genetics Sex Studies Systematic review Teenagers Triglycerides Womens health |
| title | Genetic Contribution of Variants near SORT1 and APOE on LDL Cholesterol Independent of Obesity in Children |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-06T23%3A44%3A05IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Genetic%20Contribution%20of%20Variants%20near%20SORT1%20and%20APOE%20on%20LDL%20Cholesterol%20Independent%20of%20Obesity%20in%20Children&rft.jtitle=PloS%20one&rft.au=Breitling,%20Clara&rft.date=2015-09-16&rft.volume=10&rft.issue=9&rft.spage=e0138064&rft.epage=e0138064&rft.pages=e0138064-e0138064&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0138064&rft_dat=%3Cgale_plos_%3EA428834118%3C/gale_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1719285281&rft_id=info:pmid/26375028&rft_galeid=A428834118&rft_doaj_id=oai_doaj_org_article_cc541f87c50140c3b1c8ea19bf570298&rfr_iscdi=true |