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Artikel des Monats
Verdächtige Fette – Genabschnitte für Herzerkrankungen
erkannt
In einer ausgedehnten Studie unter Federführung von Wissenschaftlern
der Medizinischen Fakultät Leipzig und des Universitätsklinikums
konnte erstmals ein Zusammenhang zwischen bestimmten genetischen Faktoren
gezeigt werden, die gleichzeitig den Anteil von pflanzlichen Sterolen
im Blut und die koronare Herzerkrankung beeinflussen. Diese Daten sind
von Bedeutung, weil pflanzliche Sterole häufig in Lebensmitteln
zugesetzt werden. Bei Menschen mit bestimmten genetischen Konstellationen
könnte dies negative Auswirkungen auf die Gesundheit haben.
Zur Pressemeldung...
Genetic Regulation of Serum Phytosterol Levels and
Risk of Coronary Artery Disease.
Teupser D, Baber R, Ceglarek U, Scholz M, Illig T,
Gieger C, Holdt LM, Leichtler A, Greiser KH, Huster D, Linsel-Nitschke
P, Schäfer A, Braund PS, Tiret L, Stark K, Raaz-Schrauder
D, Fiedler GM, Wilfert W, Beutner F, Gielen S, Großhennig
A, König IR, Lichtner P, Heid IM, Kluttig A, El Mokhtari
NE, Rubin D, Ekici AB, Reis A, Garlichs C, Hall AS, Matthes
G, Wittekind C, Hengstenberg C, Cambien F, Schreiber S, Werdan
K, Meitinger T, Löffler M, Samani NJ, Erdmann J, Wichmann
HE, Schunkert H, Thiery J.
University Leipzig, Leipzig, Germany
Circ Cardiovasc Genet. 2010 Jun 7. [Epub ahead of print]
Abstract
BACKGROUND: -Phytosterols are plant-derived sterols,
which 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 phytosterol-serum
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 (n=1495) with subsequent
replication in two additional samples (n=1157 and n=1760). Replicated
SNPs were tested for association with premature CAD in a meta-analysis
of 11 different samples comprising a total of 13,764 CAD cases
and 13,630 healthy controls. Genetic variants in the ATP-binding
cassette transporter ABCG8 and at the blood group ABO locus were
significantly associated with serum phytosterols. Effects in
ABCG8 were independently related to SNP rs4245791 and rs41360247
(combined p=1.6x10(-50) and 6.2x10(-25), respectively, n=4412).
Serum campesterol was elevated 12 degrees percent for each rs4245791
T-allele. The same allele was associated with 40 percent 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,
OR=1.10, 95%CI 1.06-1.14, p=2.2x10(-6); rs657152, OR=1.13; 95%CI
1.07-1.19, p=9.4x10(-6)), whereas alleles at ABCG8 associated
with reduced phytosterol levels were associated with reduced
CAD risk (rs41360247, OR=0.84, 95%CI 0.78-0.91, p=1.3x10(-5)).
CONCLUSIONS: -Common variants in ABCG8 and ABO are strongly associated
with serum phytosterol levels and show concordant and previously
unknown associations with CAD.
Sonderdrucke können im Referat Forschung
angefordert werden.
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