title: 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.
authors.affiliation: Centre for Public Health, Queen’s University Belfast, Belfast, Northern Ireland. g.j.mckay@qub.ac.uk
authors.forename: Gareth J
authors.initials: GJ
authors.lastname: McKay
authors.forename: Giuliana
authors.initials: G
authors.lastname: Silvestri
authors.forename: Usha
authors.initials: U
authors.lastname: Chakravarthy
authors.forename: Shilpa
authors.initials: S
authors.lastname: Dasari
authors.forename: Lars G
authors.initials: LG
authors.lastname: Fritsche
authors.forename: Bernhard H
authors.initials: BH
authors.lastname: Weber
authors.forename: Claudia N
authors.initials: CN
authors.lastname: Keilhauer
authors.forename: Michael L
authors.initials: ML
authors.lastname: Klein
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Francis
authors.forename: Caroline C
authors.initials: CC
authors.lastname: Klaver
authors.forename: Johannes R
authors.initials: JR
authors.lastname: Vingerling
authors.forename: Lintje
authors.initials: L
authors.lastname: Ho
authors.forename: Paulus T D V
authors.initials: PT
authors.lastname: De Jong
authors.forename: Michael
authors.initials: M
authors.lastname: Dean
authors.forename: Julie
authors.initials: J
authors.lastname: Sawitzke
authors.forename: Paul N
authors.initials: PN
authors.lastname: Baird
authors.forename: Robyn H
authors.initials: RH
authors.lastname: Guymer
authors.forename: Dwight
authors.initials: D
authors.lastname: Stambolian
authors.forename: Anton
authors.initials: A
authors.lastname: Orlin
authors.forename: Johanna M
authors.initials: JM
authors.lastname: Seddon
authors.forename: Inga
authors.initials: I
authors.lastname: Peter
authors.forename: Alan F
authors.initials: AF
authors.lastname: Wright
authors.forename: Caroline
authors.initials: C
authors.lastname: Hayward
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Lotery
authors.forename: Sarah
authors.initials: S
authors.lastname: Ennis
authors.forename: Michael B
authors.initials: MB
authors.lastname: Gorin
authors.forename: Daniel E
authors.initials: DE
authors.lastname: Weeks
authors.forename: Chia-Ling
authors.initials: CL
authors.lastname: Kuo
authors.forename: Aroon D
authors.initials: AD
authors.lastname: Hingorani
authors.forename: Reecha
authors.initials: R
authors.lastname: Sofat
authors.forename: Valentina
authors.initials: V
authors.lastname: Cipriani
authors.forename: Anand
authors.initials: A
authors.lastname: Swaroop
authors.forename: Mohammad
authors.initials: M
authors.lastname: Othman
authors.forename: Atsuhiro
authors.initials: A
authors.lastname: Kanda
authors.forename: Wei
authors.initials: W
authors.lastname: Chen
authors.forename: Goncalo R
authors.initials: GR
authors.lastname: Abecasis
authors.forename: John R
authors.initials: JR
authors.lastname: Yates
authors.forename: Andrew R
authors.initials: AR
authors.lastname: Webster
authors.forename: Anthony T
authors.initials: AT
authors.lastname: Moore
authors.forename: Johan H
authors.initials: JH
authors.lastname: Seland
authors.forename: Mati
authors.initials: M
authors.lastname: Rahu
authors.forename: Gisele
authors.initials: G
authors.lastname: Soubrane
authors.forename: Laura
authors.initials: L
authors.lastname: Tomazzoli
authors.forename: Fotis
authors.initials: F
authors.lastname: Topouzis
authors.forename: Jesus
authors.initials: J
authors.lastname: Vioque
authors.forename: Ian S
authors.initials: IS
authors.lastname: Young
authors.forename: Astrid E
authors.initials: AE
authors.lastname: Fletcher
authors.forename: Chris C
authors.initials: CC
authors.lastname: Patterson
mesh_terms: D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D001057:Apolipoproteins E / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D006801:Humans; D008136:Longevity / Q000235:genetics; D008268:Macular Degeneration / Q000453:epidemiology* / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D044465:White People / Q000235:genetics*
chemical_list: D001057:Apolipoproteins E