Teupser, Daniel and Baber, Ronny and Ceglarek, Uta and Scholz, Markus and Illig, Thomas and Gieger, Christian and Holdt, Lesca M. and Leichtle, Alexander and Greiser, Karin H. and Huster, Dominik and Linsel-Nitschke, Patrick and Schaefer, Arne and Braund, Peter S. and Tiret, Laurence and Stark, Klaus and Raaz-Schrauder, Dorette and Fiedler, Georg M. and Wilfert, Wolfgang and Beutner, Frank and Gielen, Stephan and Grosshennig, Anika and Koenig, Inke R. and Lichtner, Peter and Heid, Iris M. and Kluttig, Alexander and El Mokhtari, Nour E. and Rubin, Diana and Ekici, Arif B. and Reis, Andre and Garlichs, Christoph D. and Hall, Alistair S. and Matthes, Gert and Wittekind, Christian and Hengstenberg, Christian and Cambien, Francois and Schreiber, Stefan and Werdan, Karl and Meitinger, Thomas and Loeffler, Markus and Samani, Nilesh J. and Erdmann, Jeanette and Wichmann, H. -Erich and Schunkert, Heribert and Thiery, Joachim (2010) Genetic Regulation of Serum Phytosterol Levels and Risk of Coronary Artery Disease. CIRCULATION-CARDIOVASCULAR GENETICS, 3 (4). pp. 331-339. ISSN 1942-325X,
Full text not available from this repository. (Request a copy)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) (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 = 9.4 x 10(-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. (Circ Cardiovasc Genet. 2010;3:331-339.)
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | GENOME-WIDE ASSOCIATION; CARDIOVASCULAR MUNSTER PROCAM; 10000 ADULT MALES; MYOCARDIAL-INFARCTION; HEART-DISEASE; BLOOD-GROUPS; CHOLESTEROL ABSORPTION; VASCULAR-DISEASE; PLANT STEROL; ABCG8; coronary disease; genes; genetics; lipids |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Innere Medizin II Medicine > Institut für Epidemiologie und Präventivmedizin |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 20 Jul 2020 07:17 |
| Last Modified: | 20 Jul 2020 07:17 |
| URI: | https://pred.uni-regensburg.de/id/eprint/24363 |
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