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.
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.
Authors: Jessica P Otis; Meng-Chieh Shen; Blake A Caldwell; Oscar E Reyes Gaido; Steven A Farber Journal: Am J Physiol Gastrointest Liver Physiol Date: 2019-01-10 Impact factor: 4.052
Authors: Peter J H Jones; Maryam Shamloo; Dylan S MacKay; Todd C Rideout; Semone B Myrie; Jogchum Plat; Jean-Baptiste Roullet; David J Baer; Kara L Calkins; Harry R Davis; P Barton Duell; Henry Ginsberg; Helena Gylling; David Jenkins; Dieter Lütjohann; Mohammad Moghadasian; Robert A Moreau; David Mymin; Richard E Ostlund; Rouyanne T Ras; Javier Ochoa Reparaz; Elke A Trautwein; Stephen Turley; Tim Vanmierlo; Oliver Weingärtner Journal: Nutr Rev Date: 2018-10-01 Impact factor: 7.110
Authors: Peter Almgren; Andreas Lindqvist; Ulrika Krus; Liisa Hakaste; Emilia Ottosson-Laakso; Olof Asplund; Emily Sonestedt; Rashmi B Prasad; Esa Laurila; Marju Orho-Melander; Olle Melander; Tiinamaija Tuomi; Jens Juul Holst; Peter M Nilsson; Nils Wierup; Leif Groop; Emma Ahlqvist Journal: JCI Insight Date: 2017-11-02
Authors: Ariel Brautbar; Emili Leary; Kristen Rasmussen; Don P Wilson; Robert D Steiner; Salim Virani Journal: Curr Atheroscler Rep Date: 2015-04 Impact factor: 5.113