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Silbernagel, G; Chapman, MJ; Genser, B; Kleber, ME; Fauler, G; Scharnagl, H; Grammer, TB; Boehm, BO; Mäkelä, KM; Kähönen, M; Carmena, R; Rietzschel, ER; Bruckert, E; Deanfield, JE; Miettinen, TA; Raitakari, OT; Lehtimäki, T; März, W.
High intestinal cholesterol absorption is associated with cardiovascular disease and risk alleles in ABCG8 and ABO: evidence from the LURIC and YFS cohorts and from a meta-analysis.
J Am Coll Cardiol. 2013; 62(4):291-299
Doi: 10.1016/j.jacc.2013.01.100
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- Führende Autor*innen der Med Uni Graz
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Silbernagel Günther
- Co-Autor*innen der Med Uni Graz
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Fauler Günter
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März Winfried
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Scharnagl Hubert
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- Abstract:
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This study sought to determine whether high intestinal cholesterol absorption represents a cardiovascular risk factor and to link ABCG8 and ABO variants to cardiovascular disease (CVD).
Plant sterol-enriched functional foods are widely used for cholesterol lowering. Their regular intake yields a 2-fold increase in circulating plant sterol levels that equally represent markers of cholesterol absorption. Variants in ABCG8 and ABO have been associated with circulating plant sterol levels and CVD, thereby suggesting atherogenic effects of plant sterols or of cholesterol uptake.
The cholestanol-to-cholesterol ratio (CR) was used as an estimate of cholesterol absorption because it is independent of plant sterols. First, we investigated the associations of 6 single nucleotide polymorphisms in ABCG8 and ABO with CR in the LURIC (LUdwisghafen RIsk and Cardiovascular health study) and the YFS (Young Finns Study) cohorts. Second, we conducted a systematic review and meta-analysis to investigate whether CR might be related to CVD.
In LURIC, the minor alleles of rs4245791 and rs4299376 and the major alleles of rs41360247, rs6576629, and rs4953023 of the ABCG8 gene and the minor allele of rs657152 of the ABO gene were significantly associated with higher CR. Consistent results were obtained for rs4245791, rs4299376, rs6576629, and rs4953023 in YFS. The meta-analysis, including 6 studies and 4,362 individuals, found that CR was significantly increased in individuals with CVD.
High cholesterol absorption is associated with risk alleles in ABCG8 and ABO and with CVD. Harm caused by elevated cholesterol absorption rather than by plant sterols may therefore mediate the relationships of ABCG8 and ABO variants with CVD.
Copyright © 2013 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.
- Find related publications in this database (using NLM MeSH Indexing)
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ABO Blood-Group System - genetics
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ATP-Binding Cassette Transporters - genetics
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Adult -
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Aged -
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Alleles -
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Cardiovascular Diseases - genetics Cardiovascular Diseases - metabolism
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Cholesterol - metabolism
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Cohort Studies -
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Cross-Sectional Studies -
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Female -
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Follow-Up Studies -
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Humans -
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Intestinal Absorption - physiology
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Male -
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Middle Aged -
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Population Surveillance - methods
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Prospective Studies -
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Risk Factors -
- Find related publications in this database (Keywords)
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ABCG8
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ABO
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cardiovascular disease
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cholestanol
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intestinal cholesterol absorption
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plant sterols