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Articles by K Stark
Total Records ( 1 ) for K Stark
  D Teupser , R Baber , U Ceglarek , M Scholz , T Illig , C Gieger , L. M Holdt , A Leichtle , K. H Greiser , D Huster , P Linsel Nitschke , A Schafer , P. S Braund , L Tiret , K Stark , D Raaz Schrauder , G. M Fiedler , W Wilfert , F Beutner , S Gielen , A Grosshennig , I. R Konig , P Lichtner , I. M Heid , A Kluttig , N. E El Mokhtari , D Rubin , A. B Ekici , A Reis , C. D Garlichs , A. S Hall , G Matthes , C Wittekind , C Hengstenberg , F Cambien , S Schreiber , K Werdan , T Meitinger , M Loeffler , N. J Samani , J Erdmann , H. E Wichmann , H Schunkert and J. Thiery
  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=1.6x10–50 and 6.2x10–25, 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=2.2x10–6; rs657152 odds ratio, 1.13; 95% CI, 1.07 to 1.19; P=9.4x10–6), 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=1.3x10–5).

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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