Variations in apolipoprotein E frequency with age in a pooled analysis of a large group of older people

Variation in the apolipoprotein E gene (APOE) has been reported to be associated with longevity in humans. The authors assessed the allelic distribution of APOE isoforms ?2, ?3, and ?4 among 10,623 participants from 15 case-control and cohort studies of age-related macular degeneration (AMD) in populations of European ancestry (study dates ranged from 1990 to 2009). The authors included only the 10,623 control subjects from these studies who were classified as having no evidence of AMD, since variation within the APOE gene has previously been associated with AMD. In an analysis stratified by study center, gender, and smoking status, there was a decreasing frequency of the APOE ?4 isoform with increasing age (?(2) for trend = 14.9 (1 df); P = 0.0001), with a concomitant increase in the ?3 isoform (?(2) for trend = 11.3 (1 df); P = 0.001). The association with age was strongest in ?4 homozygotes; the frequency of ?4 homozygosity decreased from 2.7% for participants aged 60 years or less to 0.8% for those over age 85 years, while the proportion of participants with the ?3/?4 genotype decreased from 26.8% to 17.5% across the same age range. Gender had no significant effect on the isoform frequencies. This study provides strong support for an association of the APOE gene with human longevit