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Implications of apolipoprotein E genotype on inflammation and vitamin E status
Author(s) -
Huebbe Patricia,
Lodge John K.,
Rimbach Gerald
Publication year - 2010
Publication title -
molecular nutrition and food research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.495
H-Index - 131
eISSN - 1613-4133
pISSN - 1613-4125
DOI - 10.1002/mnfr.200900398
Subject(s) - apolipoprotein e , inflammation , vitamin e , endocrinology , tumor necrosis factor alpha , medicine , genotype , biology , proinflammatory cytokine , transactivation , calcitriol receptor , immunology , vitamin d and neurology , transcription factor , biochemistry , disease , gene , antioxidant
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 α‐tocopherol (α‐TOH) concentrations in apoE4 compared with apoE3 mice. Furthermore, genes encoding for proteins involved in peripheral α‐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 α‐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‐κB accompanied by a higher production of pro‐inflammatory molecules (tumor necrosis factor α, interleukin 1β, macrophage inflammatory protein 1‐α) 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.