ASSOCIATIONS OF Genetic Isoforms with Longevity and Risk of Mortality in Human Populations

The influence of hereditary factors on life expectancy up to 60 years of age is rather insignificant, but increases at older ages. Identification of the association of genetic variants with life expectancy and susceptibility to age-related diseases is necessary in the context of genetic heterogeneity of human populations living in different environmental conditions. In this regard, the apolipoprotein E () gene is of particular interest. This review analyzes the role of different alleles/genotypes for age attainment and associations with longevity in human populations. The ε4 allele is a strictly established genetic risk factor for Alzheimers disease (AD) in Eurasian populations, and its frequency is significantly reduced in most longevity groups compared to the general population. The rarer ε2 allele is associated with a reduced risk of AD and longevity, as it is more frequent in most longevity groups than in healthy middle-aged individuals. It is of interest to determine whether the different representation of alleles in long-livers, compared with the general population, is dependent or independent of the effect of on the risk of AD or other diseases; what is the role of the genotype on late-life attainment in African populations living in a different setting and in whom a strict association of the ε4 allele with AD has not been found. The questions of at what biological age the ε4 and ε2 alleles have a significant effect on mortality risk are addressed, as well as the role of genetic factors that have a negative or positive effect on the manifestation of the ε4 allele and associated life expectancy.