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Teupser, D.* ; Baber, R.* ; Ceglarek, U.* ; Scholz, M.* ; Illig, T. ; Gieger, C. ; Holdt, L.M.* ; Leichtle, A.* ; Greiser, K.H.* ; Huster, D.* ; Linsel-Nitschke, P.* ; Schäfer, A.* ; Braund, P.S.* ; Tiret, L.* ; Stark, K.* ; Raaz-Schrauder, D.* ; Fiedler, G.M.* ; Wilfert, W.* ; Beutner, F.* ; Gielen, S.* ; Grosshennig, A.* ; König, I.R.* ; Lichtner, P. ; Heid, I.M. ; Kluttig, A.* ; El Mokhtari, N.E.* ; Rubin, D.* ; Ekici, A.B.* ; Reis, A.* ; Garlichs, C.D. ; Hall, A.S.* ; Matthes, G.* ; Wittekind, C.* ; Hengstenberg, C.* ; Cambien, F.* ; Schreiber, S.* ; Werdan, K.* ; Meitinger, T. ; Loeffler, M.* ; Samani, N.J.* ; Erdmann, J.* ; Wichmann, H.-E. ; Schunkert, H.* ; Thiery, J.*

Genetic regulation of serum phytosterol levels and risk of coronary artery disease.

Circ. Cardiovasc. Genet. 3, 331-339 (2010)
DOI PMC
Open Access Green möglich sobald Postprint bei der ZB eingereicht worden ist.
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) (n=1495) with subsequent replication in 2 additional samples (n=1157 and n=1760). Replicated single-nucleotide polymorphisms (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 P=1.6 x 10(-50) and 6.2 x 10(-25), respectively; n=4412). Serum campesterol was elevated 12% for each rs4245791 T-allele. The same allele was associated with 40% decreased hepatic ABCG8 mRNA expression (P=0.009). Effects at the ABO locus were related to SNP rs657152 (combined P=9.4x10(-13)). Alleles of ABCG8 and ABO associated with elevated phytosterol levels displayed significant associations with increased CAD risk (rs4245791 odds ratio, 1.10; 95% CI, 1.06 to 1.14; P=2.2 x 10(-6); rs657152 odds ratio, 1.13; 95% CI, 1.07 to 1.19; P=9.4 x 10(-6)), whereas alleles at ABCG8 associated with reduced phytosterol levels were associated with reduced CAD risk (rs41360247 odds ratio, 0.84; 95% CI, 0.78 to 0.91; P=1.3 x 10(-5)). CONCLUSION: Common variants in ABCG8 and ABO are strongly associated with serum phytosterol levels and show concordant and previously unknown associations with CAD.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
Schlagwörter Coronary disease; Genes; Genetics; Lipids
ISSN (print) / ISBN 1942-325X
e-ISSN 1942-3268
Zeitschrift Circulation: Cardiovascular Genetics
Quellenangaben Band: 3, Heft: 4, Seiten: 331-339 Artikelnummer: , Supplement: ,
Verlag Lippincott Williams & Wilkins
Verlagsort Hagerstown, Md
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Epidemiology (EPI)
Institute of Human Genetics (IHG)