Replication studies in longevity: puzzling findings in Danish centenariansat the 3 ' APOB-VNTR locus

In Danes we replicated the 3'APOB-VNTR gene/longevity association study pre viously carried out in Italians, by which the Small alleles (less than 35 r epeats) had been identified as frailty alleles for longevity. In Danes, nei ther genotype nor allele frequencies differed between centenarians and 20-6 4- year-old subjects. However, when Danish and Italian data were compared, a significant difference (p = 0.0004) was found between the frequencies of Small alleles in youths, which disappeared in centenarians (p = 0.290). Fur thermore, the demographic-genetic ap roach revealed p in T)Danes a signific ant gene-sex interaction relevant to Long alleles (more than 37 repeats). T he different findings in Denmark and Italy suggest that gene/longevity asso ciations are population-specific, and heavily affected by the population-sp ecific genetic and environmental history.