Loading…
APOE ε4 is associated with higher vitamin D levels in targeted replacement mice and humans
ABSTRACT The allele ε4 of apolipoprotein E (APOE), which is a key regulator of lipid metabolism, represents a risk factor for cardiovascular diseases and Alzheimer's disease. Despite its adverse effects, the allele is common and shows a nonrandom global distribution that is thought to be the re...
Saved in:
| Published in: | The FASEB journal 2011-09, Vol.25 (9), p.3262-3270 |
|---|---|
| Main Authors: | , , , , , , , , , , , |
| Format: | Article |
| Language: | English |
| Subjects: | |
| Online Access: | Get full text |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| cited_by | |
|---|---|
| cites | |
| container_end_page | 3270 |
| container_issue | 9 |
| container_start_page | 3262 |
| container_title | The FASEB journal |
| container_volume | 25 |
| creator | Huebbe, Patricia Nebel, Almut Siegert, Sabine Moehring, Jennifer Boesch‐Saadatmandi, Christine Most, Erika Pallauf, Josef Egert, Sarah Müller, Manfred James Schreiber, Stefan Nöthlings, Ute Rimbach, Gerald |
| description | ABSTRACT
The allele ε4 of apolipoprotein E (APOE), which is a key regulator of lipid metabolism, represents a risk factor for cardiovascular diseases and Alzheimer's disease. Despite its adverse effects, the allele is common and shows a nonrandom global distribution that is thought to be the result of evolutionary adaptation. One hypothesis proposes that the APOE ε4 allele protects against vitamin D deficiency. Here we present, for the first time, experimental and epidemiological evidence that the APOE ε4 allele is indeed associated with higher serum vitamin D [25(OH)D] levels. In APOE4 targeted replacement mice, significantly higher 25(OH)D levels were found compared with those in APOE2 and APOE3 mice (70.9 vs. 41.8 and 27.8 nM, P |
| doi_str_mv | 10.1096/fj.11-180935 |
| format | article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_proquest_miscellaneous_887507715</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>887507715</sourcerecordid><originalsourceid>FETCH-LOGICAL-p1738-f682caccef0168e4de41c4926d50040cd0e25d56e9ba00fcc59b17df6d3fcc643</originalsourceid><addsrcrecordid>eNo9kLFOwzAQhi0EoqWwMSNvTCnnJHacsZQWkCoVCZgYLNe-NK6StMRJqz4Yr8EzkarAdHf6P51-fYRcMxgySMVdthoyFjAJacRPSJ_xCAIhBZySPsg0DISIZI9ceL8CAAZMnJNeyARPOY_75GP0Mp_Q76-YOk-192vjdIOW7lyT09wtc6zp1jW6dBV9oAVusfC02xtdL_EA1rgptMESq4aWziDVlaV5W-rKX5KzTBcer37ngLxPJ2_jp2A2f3wej2bBhiWRDDIhQ6ONwawrJzG2GDMTp6GwHCAGYwFDbrnAdKEBMmN4umCJzYSNukPE0YDcHv9u6vVni75RpfMGi0JXuG69kjLhkCSdmQG5-SXbRYlWbWpX6nqv_nx0QHIEdq7A_X_OQB1cq2ylGFNH12r6eh9C2HVMIZLRD-JycrA</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>887507715</pqid></control><display><type>article</type><title>APOE ε4 is associated with higher vitamin D levels in targeted replacement mice and humans</title><source>Wiley</source><creator>Huebbe, Patricia ; Nebel, Almut ; Siegert, Sabine ; Moehring, Jennifer ; Boesch‐Saadatmandi, Christine ; Most, Erika ; Pallauf, Josef ; Egert, Sarah ; Müller, Manfred James ; Schreiber, Stefan ; Nöthlings, Ute ; Rimbach, Gerald</creator><creatorcontrib>Huebbe, Patricia ; Nebel, Almut ; Siegert, Sabine ; Moehring, Jennifer ; Boesch‐Saadatmandi, Christine ; Most, Erika ; Pallauf, Josef ; Egert, Sarah ; Müller, Manfred James ; Schreiber, Stefan ; Nöthlings, Ute ; Rimbach, Gerald</creatorcontrib><description>ABSTRACT
The allele ε4 of apolipoprotein E (APOE), which is a key regulator of lipid metabolism, represents a risk factor for cardiovascular diseases and Alzheimer's disease. Despite its adverse effects, the allele is common and shows a nonrandom global distribution that is thought to be the result of evolutionary adaptation. One hypothesis proposes that the APOE ε4 allele protects against vitamin D deficiency. Here we present, for the first time, experimental and epidemiological evidence that the APOE ε4 allele is indeed associated with higher serum vitamin D [25(OH)D] levels. In APOE4 targeted replacement mice, significantly higher 25(OH)D levels were found compared with those in APOE2 and APOE3 mice (70.9 vs. 41.8 and 27.8 nM, P<0.05). Furthermore, multivariate adjusted models show a positive association of the APOE ε4 allele with 25(OH)D levels in a small collective of human subjects (n=93; P=0.072) and a general population sample (n=699; P=0.003). The novel link suggests ε4 as a modulator of vitamin D status. Although this result agrees well with evolutionary aspects, it appears contradictory with regard to chronic diseases, especially cardiovascular disease. Large prospective cohort studies are now needed to investigate the potential implications of this finding for chronic disease risks.—Huebbe, P., Nebel, A., Siegert, S., Moehring, J., Boesch‐Saadatmandi, C., Most, E., Pallauf, J., Egert, S., Müller, M. J., Schreiber, S., Nöthlings, U., Rimbach, G. APOE ε4 is associated with higher vitamin D levels in targeted replacement mice and humans. FASEB J. 25, 3262‐3270 (2011). www.fasebj.org</description><identifier>ISSN: 0892-6638</identifier><identifier>EISSN: 1530-6860</identifier><identifier>DOI: 10.1096/fj.11-180935</identifier><identifier>PMID: 21659554</identifier><language>eng</language><publisher>United States</publisher><subject>Adult ; Aged ; Alleles ; Animals ; apolipoprotein E ; Apolipoprotein E4 - genetics ; Apolipoprotein E4 - metabolism ; Calcium - metabolism ; evolutionary advantage ; Female ; Genotype ; global allele distribution ; Homeostasis ; Humans ; Male ; Mice ; Mice, Transgenic ; Middle Aged ; Vitamin D - blood ; ε4 allele</subject><ispartof>The FASEB journal, 2011-09, Vol.25 (9), p.3262-3270</ispartof><rights>2011 FASEB</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/21659554$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Huebbe, Patricia</creatorcontrib><creatorcontrib>Nebel, Almut</creatorcontrib><creatorcontrib>Siegert, Sabine</creatorcontrib><creatorcontrib>Moehring, Jennifer</creatorcontrib><creatorcontrib>Boesch‐Saadatmandi, Christine</creatorcontrib><creatorcontrib>Most, Erika</creatorcontrib><creatorcontrib>Pallauf, Josef</creatorcontrib><creatorcontrib>Egert, Sarah</creatorcontrib><creatorcontrib>Müller, Manfred James</creatorcontrib><creatorcontrib>Schreiber, Stefan</creatorcontrib><creatorcontrib>Nöthlings, Ute</creatorcontrib><creatorcontrib>Rimbach, Gerald</creatorcontrib><title>APOE ε4 is associated with higher vitamin D levels in targeted replacement mice and humans</title><title>The FASEB journal</title><addtitle>FASEB J</addtitle><description>ABSTRACT
The allele ε4 of apolipoprotein E (APOE), which is a key regulator of lipid metabolism, represents a risk factor for cardiovascular diseases and Alzheimer's disease. Despite its adverse effects, the allele is common and shows a nonrandom global distribution that is thought to be the result of evolutionary adaptation. One hypothesis proposes that the APOE ε4 allele protects against vitamin D deficiency. Here we present, for the first time, experimental and epidemiological evidence that the APOE ε4 allele is indeed associated with higher serum vitamin D [25(OH)D] levels. In APOE4 targeted replacement mice, significantly higher 25(OH)D levels were found compared with those in APOE2 and APOE3 mice (70.9 vs. 41.8 and 27.8 nM, P<0.05). Furthermore, multivariate adjusted models show a positive association of the APOE ε4 allele with 25(OH)D levels in a small collective of human subjects (n=93; P=0.072) and a general population sample (n=699; P=0.003). The novel link suggests ε4 as a modulator of vitamin D status. Although this result agrees well with evolutionary aspects, it appears contradictory with regard to chronic diseases, especially cardiovascular disease. Large prospective cohort studies are now needed to investigate the potential implications of this finding for chronic disease risks.—Huebbe, P., Nebel, A., Siegert, S., Moehring, J., Boesch‐Saadatmandi, C., Most, E., Pallauf, J., Egert, S., Müller, M. J., Schreiber, S., Nöthlings, U., Rimbach, G. APOE ε4 is associated with higher vitamin D levels in targeted replacement mice and humans. FASEB J. 25, 3262‐3270 (2011). www.fasebj.org</description><subject>Adult</subject><subject>Aged</subject><subject>Alleles</subject><subject>Animals</subject><subject>apolipoprotein E</subject><subject>Apolipoprotein E4 - genetics</subject><subject>Apolipoprotein E4 - metabolism</subject><subject>Calcium - metabolism</subject><subject>evolutionary advantage</subject><subject>Female</subject><subject>Genotype</subject><subject>global allele distribution</subject><subject>Homeostasis</subject><subject>Humans</subject><subject>Male</subject><subject>Mice</subject><subject>Mice, Transgenic</subject><subject>Middle Aged</subject><subject>Vitamin D - blood</subject><subject>ε4 allele</subject><issn>0892-6638</issn><issn>1530-6860</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2011</creationdate><recordtype>article</recordtype><recordid>eNo9kLFOwzAQhi0EoqWwMSNvTCnnJHacsZQWkCoVCZgYLNe-NK6StMRJqz4Yr8EzkarAdHf6P51-fYRcMxgySMVdthoyFjAJacRPSJ_xCAIhBZySPsg0DISIZI9ceL8CAAZMnJNeyARPOY_75GP0Mp_Q76-YOk-192vjdIOW7lyT09wtc6zp1jW6dBV9oAVusfC02xtdL_EA1rgptMESq4aWziDVlaV5W-rKX5KzTBcer37ngLxPJ2_jp2A2f3wej2bBhiWRDDIhQ6ONwawrJzG2GDMTp6GwHCAGYwFDbrnAdKEBMmN4umCJzYSNukPE0YDcHv9u6vVni75RpfMGi0JXuG69kjLhkCSdmQG5-SXbRYlWbWpX6nqv_nx0QHIEdq7A_X_OQB1cq2ylGFNH12r6eh9C2HVMIZLRD-JycrA</recordid><startdate>201109</startdate><enddate>201109</enddate><creator>Huebbe, Patricia</creator><creator>Nebel, Almut</creator><creator>Siegert, Sabine</creator><creator>Moehring, Jennifer</creator><creator>Boesch‐Saadatmandi, Christine</creator><creator>Most, Erika</creator><creator>Pallauf, Josef</creator><creator>Egert, Sarah</creator><creator>Müller, Manfred James</creator><creator>Schreiber, Stefan</creator><creator>Nöthlings, Ute</creator><creator>Rimbach, Gerald</creator><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>7X8</scope></search><sort><creationdate>201109</creationdate><title>APOE ε4 is associated with higher vitamin D levels in targeted replacement mice and humans</title><author>Huebbe, Patricia ; Nebel, Almut ; Siegert, Sabine ; Moehring, Jennifer ; Boesch‐Saadatmandi, Christine ; Most, Erika ; Pallauf, Josef ; Egert, Sarah ; Müller, Manfred James ; Schreiber, Stefan ; Nöthlings, Ute ; Rimbach, Gerald</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-p1738-f682caccef0168e4de41c4926d50040cd0e25d56e9ba00fcc59b17df6d3fcc643</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2011</creationdate><topic>Adult</topic><topic>Aged</topic><topic>Alleles</topic><topic>Animals</topic><topic>apolipoprotein E</topic><topic>Apolipoprotein E4 - genetics</topic><topic>Apolipoprotein E4 - metabolism</topic><topic>Calcium - metabolism</topic><topic>evolutionary advantage</topic><topic>Female</topic><topic>Genotype</topic><topic>global allele distribution</topic><topic>Homeostasis</topic><topic>Humans</topic><topic>Male</topic><topic>Mice</topic><topic>Mice, Transgenic</topic><topic>Middle Aged</topic><topic>Vitamin D - blood</topic><topic>ε4 allele</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Huebbe, Patricia</creatorcontrib><creatorcontrib>Nebel, Almut</creatorcontrib><creatorcontrib>Siegert, Sabine</creatorcontrib><creatorcontrib>Moehring, Jennifer</creatorcontrib><creatorcontrib>Boesch‐Saadatmandi, Christine</creatorcontrib><creatorcontrib>Most, Erika</creatorcontrib><creatorcontrib>Pallauf, Josef</creatorcontrib><creatorcontrib>Egert, Sarah</creatorcontrib><creatorcontrib>Müller, Manfred James</creatorcontrib><creatorcontrib>Schreiber, Stefan</creatorcontrib><creatorcontrib>Nöthlings, Ute</creatorcontrib><creatorcontrib>Rimbach, Gerald</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>MEDLINE - Academic</collection><jtitle>The FASEB journal</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Huebbe, Patricia</au><au>Nebel, Almut</au><au>Siegert, Sabine</au><au>Moehring, Jennifer</au><au>Boesch‐Saadatmandi, Christine</au><au>Most, Erika</au><au>Pallauf, Josef</au><au>Egert, Sarah</au><au>Müller, Manfred James</au><au>Schreiber, Stefan</au><au>Nöthlings, Ute</au><au>Rimbach, Gerald</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>APOE ε4 is associated with higher vitamin D levels in targeted replacement mice and humans</atitle><jtitle>The FASEB journal</jtitle><addtitle>FASEB J</addtitle><date>2011-09</date><risdate>2011</risdate><volume>25</volume><issue>9</issue><spage>3262</spage><epage>3270</epage><pages>3262-3270</pages><issn>0892-6638</issn><eissn>1530-6860</eissn><abstract>ABSTRACT
The allele ε4 of apolipoprotein E (APOE), which is a key regulator of lipid metabolism, represents a risk factor for cardiovascular diseases and Alzheimer's disease. Despite its adverse effects, the allele is common and shows a nonrandom global distribution that is thought to be the result of evolutionary adaptation. One hypothesis proposes that the APOE ε4 allele protects against vitamin D deficiency. Here we present, for the first time, experimental and epidemiological evidence that the APOE ε4 allele is indeed associated with higher serum vitamin D [25(OH)D] levels. In APOE4 targeted replacement mice, significantly higher 25(OH)D levels were found compared with those in APOE2 and APOE3 mice (70.9 vs. 41.8 and 27.8 nM, P<0.05). Furthermore, multivariate adjusted models show a positive association of the APOE ε4 allele with 25(OH)D levels in a small collective of human subjects (n=93; P=0.072) and a general population sample (n=699; P=0.003). The novel link suggests ε4 as a modulator of vitamin D status. Although this result agrees well with evolutionary aspects, it appears contradictory with regard to chronic diseases, especially cardiovascular disease. Large prospective cohort studies are now needed to investigate the potential implications of this finding for chronic disease risks.—Huebbe, P., Nebel, A., Siegert, S., Moehring, J., Boesch‐Saadatmandi, C., Most, E., Pallauf, J., Egert, S., Müller, M. J., Schreiber, S., Nöthlings, U., Rimbach, G. APOE ε4 is associated with higher vitamin D levels in targeted replacement mice and humans. FASEB J. 25, 3262‐3270 (2011). www.fasebj.org</abstract><cop>United States</cop><pmid>21659554</pmid><doi>10.1096/fj.11-180935</doi><tpages>9</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0892-6638 |
| ispartof | The FASEB journal, 2011-09, Vol.25 (9), p.3262-3270 |
| issn | 0892-6638 1530-6860 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_887507715 |
| source | Wiley |
| subjects | Adult Aged Alleles Animals apolipoprotein E Apolipoprotein E4 - genetics Apolipoprotein E4 - metabolism Calcium - metabolism evolutionary advantage Female Genotype global allele distribution Homeostasis Humans Male Mice Mice, Transgenic Middle Aged Vitamin D - blood ε4 allele |
| title | APOE ε4 is associated with higher vitamin D levels in targeted replacement mice and humans |
| url | http://sfxeu10.hosted.exlibrisgroup.com/loughborough?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-07T15%3A58%3A02IST&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=APOE%20%CE%B54%20is%20associated%20with%20higher%20vitamin%20D%20levels%20in%20targeted%20replacement%20mice%20and%20humans&rft.jtitle=The%20FASEB%20journal&rft.au=Huebbe,%20Patricia&rft.date=2011-09&rft.volume=25&rft.issue=9&rft.spage=3262&rft.epage=3270&rft.pages=3262-3270&rft.issn=0892-6638&rft.eissn=1530-6860&rft_id=info:doi/10.1096/fj.11-180935&rft_dat=%3Cproquest_pubme%3E887507715%3C/proquest_pubme%3E%3Cgrp_id%3Ecdi_FETCH-LOGICAL-p1738-f682caccef0168e4de41c4926d50040cd0e25d56e9ba00fcc59b17df6d3fcc643%3C/grp_id%3E%3Coa%3E%3C/oa%3E%3Curl%3E%3C/url%3E&rft_id=info:oai/&rft_pqid=887507715&rft_id=info:pmid/21659554&rfr_iscdi=true |