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Free keywords:
Aged
Aged, 80 and over
Apolipoproteins E/*genetics
Blood Glucose/metabolism
Body Mass Index
Female
Genetic Variation
Humans
Insulin/blood
Lipids/blood
Longevity/*genetics
Longitudinal Studies
Male
Middle Aged
Phenotype
*25-hydroxyvitamin D
*apoe
*glucose
*human longevity
*mediation
Abstract:
Offspring of long-lived families are characterized by beneficial metabolic phenotypes in glucose and lipid metabolism and low 25-hydroxyvitamin D. Although the genetic basis for human longevity remains largely unclear, the contribution of variation at the APOE locus has been repeatedly demonstrated. We aimed to assess whether ApoE isoforms mark the familial longevity status in middle age and subsequently to test to what extend this association is mediated by the metabolic characteristics marking this status. From the Leiden Longevity Study (LLS), we included offspring from nonagenarian siblings and partners as controls. Using the metabolic phenotypes of familial longevity as mediators, we investigated how APOE gene variants associated with LLS offspring/control status (in 1,515 LLS offspring and 715 controls). Within the LLS (mean age = 59.2 years), ApoE epsilon4 was not associated with a lower likelihood of being an LLS offspring, whereas ApoE varepsilon2 was significantly associated with a higher likelihood of being an LLS offspring (odds ratio = 1.43), but this difference was not mediated (p-values>0.05) by any of the investigated metabolic phenotypes (e.g., diabetes and glucose). Therefore, variation at the APOE locus may not influence familial longevity status in middle age significantly through any of the metabolic mechanisms investigated.
