Tagging long-lived individuals through vitamin-D receptor (VDR) haplotypes

Longevity is a complex phenomenon involving multiple environmental and biological factors. Genetic studies of longevity have focussed on DNA repair, oxidative damage correction and immune-related genes. Vitamin-D works by modulating mineral homeostasis and key physiological processes such as cell proliferation and immune response. Vitamin-D insufficiency has been largely considered a risk factor for life-limiting illnesses including cardiovascular and immune-related diseases and cancer. Vitamin-D acts through vitamin-D-receptor (VDR), which regulates the expression of vitamin-D-response genes. VDR variants have been associated with susceptibility to cancer, bacterial and viral infections, autoimmune diseases, and allergies. In the present study we evaluated VDR as candidate gene involved in human longevity. We selected five polymorphisms of the VDR gene that capture variability at the 5', coding and 3' regions. Genotype data was obtained from 104 octogenarians (>85 years) and 114 controls (17-40 years). Although differences in genotype and allele distribution did not reach statistical significance, haplotype distribution was distinctive, mainly for 3' region haplotypes and particularly in males. Our results suggest a role for VDR gene variability in aging and longevity.