Zusammenfassung
Polymorphismen in Genen des Lipidstoffwechsels spielen in der Pathogenese von koronaren
Herz-Kreislauf-Erkrankungen (KHK) eine wichtige Rolle. Eine besondere Funktion hat
dabei das Apolipoprotein E. ApoE ist polymorph. Man unterscheidet 3 Allele, die für
die Isoformen ApoE2, ApoE3 und ApoE4 codieren. ApoE4-Träger haben ein erhöhtes Risiko
für KHK und neurodegenerative Krankheiten. Untersuchungen zeigen, dass beim ApoE4-Genotyp
sowohl die Lipidperoxidation als auch die Produktion reaktiver Sauerstoffspezies gesteigert
ist. Darüber hinaus ist dieser Risikogenotyp mit erhöhter Inflammation assoziiert,
die vermutlich auf einer gesteigerten Transaktivierung des redoxsensitiven Transkriptionsfaktors
NF-κB basiert. Studien zeigen, dass Flavonoide chronisch entzündliche Prozesse sowohl
in vitro als auch in vivo antagonisieren. Gleichermaßen sind Flavonoide Induktoren
hepatischer Paraoxonase, ein Enzym, das die LDL-Oxidation verhindert. Der ApoE3-Genotyp
ist, verglichen mit dem ApoE4-Genotyp, stärker responsiv im Hinblick auf die gesundheitsfördernden
Effekte von Flavonoiden, die in relativ hoher Konzentration in der mediterranen Ernährung
vorkommen. Diese Effekte betreffen die Entzündungshemmung, die Hemmung der LDL-Oxidation
und die Senkung des Blutdrucks.
Abstract
Polymorphisms in the genes encoding for proteins of the lipid metabolism may have
an important role in the pathogenesis of coronary heart disease (CHD). Apolipoprotein
E has a particular function in this setting. ApoE is polymorphous, and distinction
is made between 3 alleles that encode for the isoforms ApoE2, ApoE3, and ApoE4. Carriers
of ApoE4 have an increased risk for CHD and neurodegenerative diseases. Studies have
shown that for the ApoE4 genotype, lipid peroxidation and the production of reactive
oxygen species are increased. Further, this risk genotype is associated with increased
inflammation, which is thought to be based on increased transactivation of the redox-sensitive
transcription factor NF-kB. Studies have shown that flavonoids counteract inflammatory
processes in vitro as well as in vivo. Similarly, flavonoids are inductors of hepatic
paraoxonase, an enzyme that prevents LDL oxidation. The ApoE3 genotype is more responsive
than the ApoE4 genotype in terms of the health promoting effects of flavonoids, which
are present in the mediterranean diet in high concentrations. This concerns anti-inflammatory
effects, inhibition of LDL oxidation, and blood pressure lowering effects.
Schlüsselwörter
Apolipoprotein E - ApoE4-Risikogenotyp - Paraoxonase - inflammatorische Zytokine -
sekundäre Pflanzenstoffe
Keywords
apolipoprotein E - ApoE4 risk genotype - paraoxonase - inflammatory cytokines - phytochemicals
Literatur
1
Minihane A M, Jofre-Monseny L, Olano-Martin E et al.
ApoE genotype, cardiovascular risk and responsiveness to dietary fat manipulation.
Proceedings of the Nutrition Society.
2007;
66
183-197
2
Flachsbart F, Caliebe A, Kleindorp R et al.
Association of FOXO3A variation with human longevity confirmed in German centenarians.
Proc Natl Acad Sci USA.
2009;
106
2700-2705
3
Dietrich M, Hu Y, Block G et al.
Associations between Apolipoprotein E genotype and circulating F2-isoprostane levels
in humans.
Lipids.
2005;
40
329-334
4
Jofre-Monseny L, De Pascual-Teresa S, Plonka E et al.
Differential effects of apolipoprotein E3 and E4 on markers of oxidative status in
macrophages.
British Journal of Nutrition.
2007;
97
864-871
5
Caliebe A, Kleindorb R, Blanché H et al.
No or only population-specific effect of PON1 on human longevity: A comprehensive
meta-analysis.
Ageing Research Reviews.
2010;
9
238-244
6
Boesch-Saadatmandi C, Niering J, Minihane A M et al.
Impact of apolipoprotein E genotype and dietary quercetin on paraoxonase 1 status
in apoE3 and apoE4 transgenic mice.
Atherosclerosis.
2010;
211
110-113
7
Jofre-Monseny L, Loboda A, Wagner A E et al.
Effects of apo E genotype on macrophage inflammation and heme-oxygenase-1 expression.
Biochemical and Biophysical Research Communications.
2007;
357
319-324
8
Boesch-Saadatmandi C, Loboda A, Wagner A E et al.
Effect of quercetin and its metabolites isorhamnetin and quercetin-3-glucoronide on
inflammatory gene expression – role of miRNA 155.
Journal of Nutritional Biochemistry.
2010;
140
278-284
9
Boesch-Saadatmandi C, Wolffram S, Minihane A M et al.
Effect of apoE genotype and dietary quercetin on blood lipids and TNF-alpha levels
in apoE3 and apoE4 targeted gene replacement mice.
British Journal of Nutrition.
2008;
101
1440-1443
10
Egert S, Bosy-Westphal A, Seiberl J et al.
Quercetin reduces systolic blood pressure and plasma oxidised low-density lipoprotein
concentrations in overweight subjects with a high-cardiovascular disease risk phenotype:
a double-blinded, placebo-controlled cross-over study.
British Journal of Nutrition.
2009;
102
1065-1074
11
Huebbe P, Jofre-Monseny L, Rimbach G.
Alpha-tocopherol transport in the lung is affected by the apoE genotype – Studies
in transgenic apoE3 and apoE4 mice.
IUBMB Life.
2009;
61
453-456
12
Huebbe P, Lodge J K, Rimbach G.
Implications of ApoE genotype on inflammation and vitamin E status.
Molecular Nutrition and Food Research.
2010;
54
623-630
13
Minihane A M, Khan S, Leigh-Firebank E C et al.
ApoE polymorphism and fish oil supplementation in subjects with an atherogenic lipoprotein
phenotype.
Arteriosclerosis Thrombosis Vascular Biology.
2000;
20
1990-1997
Prof. Dr. Gerald Rimbach
Institut für Humanernährung und Lebensmittelkunde, Christian-Albrechts-Universität
zu Kiel
Hermann-Rodewald-Straße 6
24118 Kiel
Phone: 0431/8802583
Email: rimbach@foodsci.uni-kiel.de