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.

Silbernagel, Günther; Chapman, M John; Genser, Bernd; Kleber, Marcus E; Fauler, Günter; Scharnagl, Hubert; Grammer, Tanja B; Boehm, Bernhard O; Mäkelä, Kari-Matti; Kähönen, Mika; Carmena, Rafael; Rietzschel, Ernst R; Bruckert, Eric; Deanfield, John E; Miettinen, Tatu A; Raitakari, Olli T; Lehtimäki, Terho; März, Winfried (2013). 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. Journal of the American College of Cardiology, 62(4), pp. 291-299. Elsevier 10.1016/j.jacc.2013.01.100

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OBJECTIVES 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). BACKGROUND 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. METHODS 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. RESULTS 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. CONCLUSIONS 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.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Cardiovascular Disorders (DHGE) > Clinic of Angiology

UniBE Contributor:

Silbernagel, Günther

Subjects:

600 Technology > 610 Medicine & health

ISSN:

0735-1097

Publisher:

Elsevier

Language:

English

Submitter:

Catherine Gut

Date Deposited:

08 Jul 2014 10:36

Last Modified:

30 Oct 2015 07:34

Publisher DOI:

10.1016/j.jacc.2013.01.100

PubMed ID:

23707316

Uncontrolled Keywords:

ABCG8, ABO, CI, CVD, GWA, LDL, RR, SMD, SNP, cardiovascular disease, cholestanol, confidence interval, genome-wide association, intestinal cholesterol absorption, low-density lipoprotein, plant sterols, risk ratio, single nucleotide polymorphism, standardized mean difference

BORIS DOI:

10.7892/boris.50727

URI:

https://boris.unibe.ch/id/eprint/50727

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