Genetic Regulation of Serum Phytosterol Levels and Risk of Coronary Artery Disease

Abstract

Background—Phytosterols are plant-derived sterols that are taken up from food and can serve as biomarkers of cholesterol uptake. Serum levels are under tight genetic control. We used a genomic approach to study the molecular regulation of serum phytosterol levels and potential links to coronary artery disease (CAD). Methods and Results—A genome-wide association study for serum phytosterols (campesterol, sitosterol, brassicasterol) was conducted in a population-based sample from KORA (Cooperative Research in the Region of Augsburg) (n1495) with subsequent replication in 2 additional samples (n1157 and n1760). Replicated single-nucleotide poly-morphisms (SNPs) were tested for association with premature CAD in a metaanalysis of 11 different samples comprising 13 764 CAD cases and 13 630 healthy controls. Genetic variants in the ATP-binding hemitransporter ABCG8 and at the blood group ABO locus were significantly associated with serum phytosterols. Effects in ABCG8 were independently related to SNPs rs4245791 and rs41360247 (combined P1.61050 and 6.21025, respectively; n4412). Serum campesterol was elevated 12 % for each rs4245791 T-allele. The same allele was associated with 40% decreased hepatic ABCG8 mRNA expression (P0.009). Effects at the ABO locus were related to SNP rs657152 (combined P9.41013). Alleles of ABCG8 and ABO associated with elevated phytosterol levels displayed significan

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oai:CiteSeerX.psu:10.1.1.986.996Last time updated on 11/2/2017

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