Implications of apolipoprotein E genotype on inflammation and vitamin E status.
In Western societies the apolipoprotein E4 (apoE4) genotype is associated with increased morbidity and mortality and represents a significant risk factor for cardiovascular and Alzheimer's disease. In a recent study we observed significantly lower tissue alpha-tocopherol (alpha-TOH) concentrations in apoE4 compared with apoE3 mice. Furthermore, genes encoding for proteins involved in peripheral alpha-TOH transport and degradation were affected by the apoE genotype. Thus, the apoE4 genotype may be associated with lower vitamin E retention in peripheral tissues. This is possibly related to an altered lipoprotein metabolism including increased alpha-TOH retention in LDL, a decreased expression of lipoprotein receptors and impaired cellular vitamin E delivery system, and a greater intracellular degradation of tocopherols in the apoE4 genotype. An increasing number of studies in cultured cells, transgenic mice and human volunteers indicate a more pro-inflammatory state associated with the apoE4 allele. In apoE4 macrophages there is an enhanced transactivation of the key redox sensitive transcription factor NF-kappaB accompanied by a higher production of pro-inflammatory molecules (tumor necrosis factor alpha, interleukin 1beta, macrophage inflammatory protein 1-alpha) and a lower production of anti-inflammatory interleukin 10, as compared with apoE3 macrophages. Both tissue vitamin E retention and biomarkers of chronic inflammation may be affected by the apoE genotype.
Huebbe
Patricia
P
Institute of Human Nutrition and Food Science, Christian-Albrechts-University, Kiel, Germany.
Lodge
John K
JK
Rimbach
Gerald
G
D000544:Alzheimer Disease / Q000453:epidemiology / Q000235:genetics; D000818:Animals; D053318:Apolipoprotein E3 / Q000235:genetics / Q000378:metabolism; D053327:Apolipoprotein E4 / Q000235:genetics; D001057:Apolipoproteins E / Q000235:genetics* / Q000378:metabolism*; D002318:Cardiovascular Diseases / Q000453:epidemiology / Q000235:genetics; D005838:Genotype; D005858:Germany; D006801:Humans; D007249:Inflammation / Q000235:genetics*; D051379:Mice; D011110:Polymorphism, Genetic; D012333:RNA, Messenger / Q000235:genetics; D014810:Vitamin E / Q000378:metabolism*; D024502:alpha-Tocopherol / Q000097:blood
D053318:Apolipoprotein E3; D053327:Apolipoprotein E4; D001057:Apolipoproteins E; D012333:RNA, Messenger; D014810:Vitamin E; D024502:alpha-Tocopherol