Genetic Variation in ABC G5/G8 and NPC1L1 Impact Cholesterol Response to Plant Sterols in Hypercholesterolemic Men
ATP-binding cassette hetero-dimeric transporters G5 and G8 (ABCG5/G8) have been postulated to mediate intestinal cholesterol efflux, whereas Niemann-Pick C1 Like 1 (NPC1L1) protein is believed to be essential for intestinal cholesterol influx. The individual or combined genetic markers, such as sing...
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| Veröffentlicht in: | Lipids 2008-12, Vol.43 (12), p.1155-1164 |
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| creator | Zhao, Hai L Houweling, Adrielle H Vanstone, Catherine A Jew, Stephanie Trautwein, Elke A Duchateau, Guus S. M. J. E Jones, Peter J. H |
| description | ATP-binding cassette hetero-dimeric transporters G5 and G8 (ABCG5/G8) have been postulated to mediate intestinal cholesterol efflux, whereas Niemann-Pick C1 Like 1 (NPC1L1) protein is believed to be essential for intestinal cholesterol influx. The individual or combined genetic markers, such as single nuclear polymorphisms (SNPs), of these two transporter genes may explain inter-individual variations in plasma cholesterol response following plant sterol (PS) intervention. The present study was aimed at investigating the association between ABCG5/G8 and NPC1L1 genotype SNPs with sterol absorption and corresponding plasma concentrations. The study used a 4-week crossover design with 82 hypercholesterolemic men characterized by high vs. low basal plasma PS concentrations consuming spreads with or without 2 g/day of PS. For the ABCG8 1289 C > A (T400 K) polymorphism, the A allele carriers with high basal plasma PS concentrations demonstrated a 3.9-fold greater reduction (p < 0.05) in serum low density lipoprotein cholesterol (LDL-C) than their low basal plasma PS counterparts. For the NPC1L1 haplotype of 872 C > G (L272L) and 3929 G > A (Y1291Y), individuals carrying mutant alleles showed a 2.4-fold greater (p < 0.05) reduction in LDL-C levels, compared to wild type counterparts. Results suggest that genetic and metabolic biomarkers together may predict inter-individual lipid level responsiveness to PS-intervention, and thus could be useful in devising individualized cholesterol lowering strategies. |
| doi_str_mv | 10.1007/s11745-008-3241-y |
| format | Article |
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M. J. E ; Jones, Peter J. H</creator><creatorcontrib>Zhao, Hai L ; Houweling, Adrielle H ; Vanstone, Catherine A ; Jew, Stephanie ; Trautwein, Elke A ; Duchateau, Guus S. M. J. E ; Jones, Peter J. H</creatorcontrib><description>ATP-binding cassette hetero-dimeric transporters G5 and G8 (ABCG5/G8) have been postulated to mediate intestinal cholesterol efflux, whereas Niemann-Pick C1 Like 1 (NPC1L1) protein is believed to be essential for intestinal cholesterol influx. The individual or combined genetic markers, such as single nuclear polymorphisms (SNPs), of these two transporter genes may explain inter-individual variations in plasma cholesterol response following plant sterol (PS) intervention. The present study was aimed at investigating the association between ABCG5/G8 and NPC1L1 genotype SNPs with sterol absorption and corresponding plasma concentrations. The study used a 4-week crossover design with 82 hypercholesterolemic men characterized by high vs. low basal plasma PS concentrations consuming spreads with or without 2 g/day of PS. For the ABCG8 1289 C > A (T400 K) polymorphism, the A allele carriers with high basal plasma PS concentrations demonstrated a 3.9-fold greater reduction (p < 0.05) in serum low density lipoprotein cholesterol (LDL-C) than their low basal plasma PS counterparts. For the NPC1L1 haplotype of 872 C > G (L272L) and 3929 G > A (Y1291Y), individuals carrying mutant alleles showed a 2.4-fold greater (p < 0.05) reduction in LDL-C levels, compared to wild type counterparts. Results suggest that genetic and metabolic biomarkers together may predict inter-individual lipid level responsiveness to PS-intervention, and thus could be useful in devising individualized cholesterol lowering strategies.</description><identifier>ISSN: 0024-4201</identifier><identifier>EISSN: 1558-9307</identifier><identifier>DOI: 10.1007/s11745-008-3241-y</identifier><identifier>PMID: 18850127</identifier><language>eng</language><publisher>Berlin/Heidelberg: Berlin/Heidelberg : Springer-Verlag</publisher><subject>ABC transporters ; ATP Binding Cassette Transporter, Sub-Family G, Member 5 ; ATP Binding Cassette Transporter, Sub-Family G, Member 8 ; ATP-Binding Cassette Transporters - genetics ; ATP-Binding Cassette Transporters - metabolism ; ATP‐binding cassette G5 ; ATP‐binding cassette G8 ; Biomedical and Life Sciences ; blood plasma ; Cholesterol ; Cholesterol - metabolism ; Diet ; Genetic diversity ; Genetic markers ; genetic variation ; Haplotypes ; human genetics ; human health ; human nutrition ; Humans ; hypercholesterolemia ; Hypercholesterolemia - genetics ; Hypercholesterolemia - metabolism ; intestines ; Life Sciences ; Lipidology ; Lipoproteins - genetics ; Lipoproteins - metabolism ; low density lipoprotein ; Male ; Medical Biochemistry ; Medicinal Chemistry ; Membrane Proteins - genetics ; Membrane Proteins - metabolism ; Microbial Genetics and Genomics ; Neurochemistry ; Niemann-PickC1 like 1 ; Niemann‐Pick C1 Like 1 protein ; Nutrition ; Original Article ; physiological transport ; phytosterols ; Plant sterols ; Plants - chemistry ; Polymorphism, Single Nucleotide ; Single nuclear polymorphism ; Sterols - administration & dosage ; Sterols - metabolism</subject><ispartof>Lipids, 2008-12, Vol.43 (12), p.1155-1164</ispartof><rights>AOCS 2008</rights><rights>2008 American Oil Chemists' Society (AOCS)</rights><rights>Copyright AOCS Press Dec 2008</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c5075-a789f69f7c741a798bad7d368434c691707990dbbd978c5d02ae6ed4af204cff3</citedby><cites>FETCH-LOGICAL-c5075-a789f69f7c741a798bad7d368434c691707990dbbd978c5d02ae6ed4af204cff3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s11745-008-3241-y$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s11745-008-3241-y$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>315,781,785,1418,27929,27930,41493,42562,45579,45580,51324</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/18850127$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Zhao, Hai L</creatorcontrib><creatorcontrib>Houweling, Adrielle H</creatorcontrib><creatorcontrib>Vanstone, Catherine A</creatorcontrib><creatorcontrib>Jew, Stephanie</creatorcontrib><creatorcontrib>Trautwein, Elke A</creatorcontrib><creatorcontrib>Duchateau, Guus S. M. J. E</creatorcontrib><creatorcontrib>Jones, Peter J. H</creatorcontrib><title>Genetic Variation in ABC G5/G8 and NPC1L1 Impact Cholesterol Response to Plant Sterols in Hypercholesterolemic Men</title><title>Lipids</title><addtitle>Lipids</addtitle><addtitle>Lipids</addtitle><description>ATP-binding cassette hetero-dimeric transporters G5 and G8 (ABCG5/G8) have been postulated to mediate intestinal cholesterol efflux, whereas Niemann-Pick C1 Like 1 (NPC1L1) protein is believed to be essential for intestinal cholesterol influx. The individual or combined genetic markers, such as single nuclear polymorphisms (SNPs), of these two transporter genes may explain inter-individual variations in plasma cholesterol response following plant sterol (PS) intervention. The present study was aimed at investigating the association between ABCG5/G8 and NPC1L1 genotype SNPs with sterol absorption and corresponding plasma concentrations. The study used a 4-week crossover design with 82 hypercholesterolemic men characterized by high vs. low basal plasma PS concentrations consuming spreads with or without 2 g/day of PS. For the ABCG8 1289 C > A (T400 K) polymorphism, the A allele carriers with high basal plasma PS concentrations demonstrated a 3.9-fold greater reduction (p < 0.05) in serum low density lipoprotein cholesterol (LDL-C) than their low basal plasma PS counterparts. For the NPC1L1 haplotype of 872 C > G (L272L) and 3929 G > A (Y1291Y), individuals carrying mutant alleles showed a 2.4-fold greater (p < 0.05) reduction in LDL-C levels, compared to wild type counterparts. Results suggest that genetic and metabolic biomarkers together may predict inter-individual lipid level responsiveness to PS-intervention, and thus could be useful in devising individualized cholesterol lowering strategies.</description><subject>ABC transporters</subject><subject>ATP Binding Cassette Transporter, Sub-Family G, Member 5</subject><subject>ATP Binding Cassette Transporter, Sub-Family G, Member 8</subject><subject>ATP-Binding Cassette Transporters - genetics</subject><subject>ATP-Binding Cassette Transporters - metabolism</subject><subject>ATP‐binding cassette G5</subject><subject>ATP‐binding cassette G8</subject><subject>Biomedical and Life Sciences</subject><subject>blood plasma</subject><subject>Cholesterol</subject><subject>Cholesterol - metabolism</subject><subject>Diet</subject><subject>Genetic diversity</subject><subject>Genetic markers</subject><subject>genetic variation</subject><subject>Haplotypes</subject><subject>human genetics</subject><subject>human health</subject><subject>human nutrition</subject><subject>Humans</subject><subject>hypercholesterolemia</subject><subject>Hypercholesterolemia - genetics</subject><subject>Hypercholesterolemia - metabolism</subject><subject>intestines</subject><subject>Life Sciences</subject><subject>Lipidology</subject><subject>Lipoproteins - genetics</subject><subject>Lipoproteins - metabolism</subject><subject>low density lipoprotein</subject><subject>Male</subject><subject>Medical Biochemistry</subject><subject>Medicinal Chemistry</subject><subject>Membrane Proteins - genetics</subject><subject>Membrane Proteins - metabolism</subject><subject>Microbial Genetics and Genomics</subject><subject>Neurochemistry</subject><subject>Niemann-PickC1 like 1</subject><subject>Niemann‐Pick C1 Like 1 protein</subject><subject>Nutrition</subject><subject>Original Article</subject><subject>physiological transport</subject><subject>phytosterols</subject><subject>Plant sterols</subject><subject>Plants - chemistry</subject><subject>Polymorphism, Single Nucleotide</subject><subject>Single nuclear polymorphism</subject><subject>Sterols - administration & dosage</subject><subject>Sterols - metabolism</subject><issn>0024-4201</issn><issn>1558-9307</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2008</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><recordid>eNqFkkFv1DAUhC0EokvhB3ABi0NvoX6JHdvHNi3blRZYUcrV8jpOSZXYwc6qyr_HS1ZaiUN7six_Mx69eQi9B_IZCOHnEYBTlhEisiKnkE0v0AIYE5ksCH-JFoTkNKM5gRP0JsaHdAUq2Wt0AkIwAjlfoLC0zo6twb90aPXYeodbhy8uK7xk50uBtavxt00Fa8CrftBmxNVv39k42uA7_MPGwbto8ejxptNuxLf_HuLe5GYabDBH2vbpm6_WvUWvGt1F--5wnqK7L9c_q5ts_X25qi7WmWGEs0xzIZtSNtxwCppLsdU1r4tS0IKaUgInXEpSb7e15MKwmuTalramuskJNU1TnKKz2XcI_s8uhVB9G43tUk7rd1GVUjCaJpHAT_-BD34XXMqmck5LykrJEgQzZIKPMdhGDaHtdZgUELVvQ81tqNSG2rehpqT5cDDebXtbHxWH8SeAz8Bj29npeUe1Xm2uIFWclPmsjEnk7m04Zn4qz8dZ1Giv9H1oo7q7TetREGAlZ1AUfwEr062-</recordid><startdate>200812</startdate><enddate>200812</enddate><creator>Zhao, Hai L</creator><creator>Houweling, Adrielle H</creator><creator>Vanstone, Catherine A</creator><creator>Jew, Stephanie</creator><creator>Trautwein, Elke A</creator><creator>Duchateau, Guus S. 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M. J. E ; Jones, Peter J. H</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c5075-a789f69f7c741a798bad7d368434c691707990dbbd978c5d02ae6ed4af204cff3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2008</creationdate><topic>ABC transporters</topic><topic>ATP Binding Cassette Transporter, Sub-Family G, Member 5</topic><topic>ATP Binding Cassette Transporter, Sub-Family G, Member 8</topic><topic>ATP-Binding Cassette Transporters - genetics</topic><topic>ATP-Binding Cassette Transporters - metabolism</topic><topic>ATP‐binding cassette G5</topic><topic>ATP‐binding cassette G8</topic><topic>Biomedical and Life Sciences</topic><topic>blood plasma</topic><topic>Cholesterol</topic><topic>Cholesterol - metabolism</topic><topic>Diet</topic><topic>Genetic diversity</topic><topic>Genetic markers</topic><topic>genetic variation</topic><topic>Haplotypes</topic><topic>human genetics</topic><topic>human health</topic><topic>human nutrition</topic><topic>Humans</topic><topic>hypercholesterolemia</topic><topic>Hypercholesterolemia - genetics</topic><topic>Hypercholesterolemia - metabolism</topic><topic>intestines</topic><topic>Life Sciences</topic><topic>Lipidology</topic><topic>Lipoproteins - genetics</topic><topic>Lipoproteins - metabolism</topic><topic>low density lipoprotein</topic><topic>Male</topic><topic>Medical Biochemistry</topic><topic>Medicinal Chemistry</topic><topic>Membrane Proteins - genetics</topic><topic>Membrane Proteins - metabolism</topic><topic>Microbial Genetics and Genomics</topic><topic>Neurochemistry</topic><topic>Niemann-PickC1 like 1</topic><topic>Niemann‐Pick C1 Like 1 protein</topic><topic>Nutrition</topic><topic>Original Article</topic><topic>physiological transport</topic><topic>phytosterols</topic><topic>Plant sterols</topic><topic>Plants - chemistry</topic><topic>Polymorphism, Single Nucleotide</topic><topic>Single nuclear polymorphism</topic><topic>Sterols - administration & dosage</topic><topic>Sterols - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Zhao, Hai L</creatorcontrib><creatorcontrib>Houweling, Adrielle H</creatorcontrib><creatorcontrib>Vanstone, Catherine A</creatorcontrib><creatorcontrib>Jew, Stephanie</creatorcontrib><creatorcontrib>Trautwein, Elke A</creatorcontrib><creatorcontrib>Duchateau, Guus S. M. J. E</creatorcontrib><creatorcontrib>Jones, Peter J. 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M. J. E</au><au>Jones, Peter J. H</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Genetic Variation in ABC G5/G8 and NPC1L1 Impact Cholesterol Response to Plant Sterols in Hypercholesterolemic Men</atitle><jtitle>Lipids</jtitle><stitle>Lipids</stitle><addtitle>Lipids</addtitle><date>2008-12</date><risdate>2008</risdate><volume>43</volume><issue>12</issue><spage>1155</spage><epage>1164</epage><pages>1155-1164</pages><issn>0024-4201</issn><eissn>1558-9307</eissn><abstract>ATP-binding cassette hetero-dimeric transporters G5 and G8 (ABCG5/G8) have been postulated to mediate intestinal cholesterol efflux, whereas Niemann-Pick C1 Like 1 (NPC1L1) protein is believed to be essential for intestinal cholesterol influx. The individual or combined genetic markers, such as single nuclear polymorphisms (SNPs), of these two transporter genes may explain inter-individual variations in plasma cholesterol response following plant sterol (PS) intervention. The present study was aimed at investigating the association between ABCG5/G8 and NPC1L1 genotype SNPs with sterol absorption and corresponding plasma concentrations. The study used a 4-week crossover design with 82 hypercholesterolemic men characterized by high vs. low basal plasma PS concentrations consuming spreads with or without 2 g/day of PS. For the ABCG8 1289 C > A (T400 K) polymorphism, the A allele carriers with high basal plasma PS concentrations demonstrated a 3.9-fold greater reduction (p < 0.05) in serum low density lipoprotein cholesterol (LDL-C) than their low basal plasma PS counterparts. For the NPC1L1 haplotype of 872 C > G (L272L) and 3929 G > A (Y1291Y), individuals carrying mutant alleles showed a 2.4-fold greater (p < 0.05) reduction in LDL-C levels, compared to wild type counterparts. Results suggest that genetic and metabolic biomarkers together may predict inter-individual lipid level responsiveness to PS-intervention, and thus could be useful in devising individualized cholesterol lowering strategies.</abstract><cop>Berlin/Heidelberg</cop><pub>Berlin/Heidelberg : Springer-Verlag</pub><pmid>18850127</pmid><doi>10.1007/s11745-008-3241-y</doi><tpages>10</tpages></addata></record> |
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| subjects | ABC transporters ATP Binding Cassette Transporter, Sub-Family G, Member 5 ATP Binding Cassette Transporter, Sub-Family G, Member 8 ATP-Binding Cassette Transporters - genetics ATP-Binding Cassette Transporters - metabolism ATP‐binding cassette G5 ATP‐binding cassette G8 Biomedical and Life Sciences blood plasma Cholesterol Cholesterol - metabolism Diet Genetic diversity Genetic markers genetic variation Haplotypes human genetics human health human nutrition Humans hypercholesterolemia Hypercholesterolemia - genetics Hypercholesterolemia - metabolism intestines Life Sciences Lipidology Lipoproteins - genetics Lipoproteins - metabolism low density lipoprotein Male Medical Biochemistry Medicinal Chemistry Membrane Proteins - genetics Membrane Proteins - metabolism Microbial Genetics and Genomics Neurochemistry Niemann-PickC1 like 1 Niemann‐Pick C1 Like 1 protein Nutrition Original Article physiological transport phytosterols Plant sterols Plants - chemistry Polymorphism, Single Nucleotide Single nuclear polymorphism Sterols - administration & dosage Sterols - metabolism |
| title | Genetic Variation in ABC G5/G8 and NPC1L1 Impact Cholesterol Response to Plant Sterols in Hypercholesterolemic Men |
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