Variations in Apolipoprotein E Frequency With Age in a Pooled Analysis of a Large Group of Older People

Abstract

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 ε2, ε3, and ε4 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 ε4 isoform with increasing age (χ(2) for trend = 14.9 (1 df); P = 0.0001), with a concomitant increase in the ε3 isoform (χ(2) for trend = 11.3 (1 df); P = 0.001). The association with age was strongest in ε4 homozygotes; the frequency of ε4 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 ε3/ε4 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 longevity.

Vitellogenin in inflammation and immunity in social insects

“…Strikingly, greatly elevated levels of the evolutionarily related apolipoprotein B and its susceptibility to oxidation is notoriously linked to atherosclerosis in humans [64] . However, human studies manifest that it is the balance of various lipoproteins in blood that is key in extreme longevity in humans [65][66][67] .…”

Evidence from case–control and longitudinal studies supports associations of genetic variation in APOE, CETP, and IL6 with human longevity

“…The APOE ε4 haplotype is by far the most validated genetic variation and has repeatedly been associated with human longevity (e.g., Asada et al 1996;Bathum et al 2006;Deelen et al 2011;Gerdes et al 2000;McKay et al 2011;Nebel et al 2011;Schachter et al 1994), whereas one study has found association of rs2542052 in APOC3 with longevity (Atzmon et al 2006). The APOE polymorphism was recently reviewed in (Seripa et al 2011).…”

“…These studies include rs2542052 in APOC3 (Novelli et al 2008), rs5882 in CETP (Cellini et al 2005;Novelli et al 2008), I/D insertion/deletion in ACE (Agerholm-Larsen et al 1997;Bladbjerg et al 1999;Blanche et al 2001;Yang et al 2009), rs1800562 in HFE (Carru et al 2003;Coppin et al 2003), and rs180113 in MTHFR (Bladbjerg et al 1999;Khabour et al 2009;Hessner et al 2001;Brattstrom et al 1998) and−176C/G in IL6 (Pes et al 2004;Wang et al 2001). Furthermore, a few meta-analyses or pooled analyses have been published; for APOE ε4 and the ACE I/D, insertion/deletion association was supported (McKay et al 2011;Zajc et al 2012), while for the IL6 −176C/G polymorphism, a North/South European gradient of association was suggested (Di Bona et al 2009). In any case, the involvement in longevity of the majority of these specific polymorphisms still remains uncertain.…”

Clinical presentation of chronic traumatic encephalopathy

“…Chi-square analyses were used for between group comparisons for categorical data. APOE genotype analyses comparing CTE cases with population norms 17 were conducted with the x 2 goodness-of-fit test. A probability level of p 5 0.05 was used throughout.…”