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

Gareth J. McKay, Giuliana Silvestri, Usha Chakravarthy, Shilpa Dasari, Lars G. Fritsche, Bernhard H. Weber, Claudia N. Keilhauer, Michael L. Klein, Peter J. Francis, Caroline C. Klaver, Johannes R. Vingerling, Lintje Ho, Paulus T.D.V. De Jong, Michael Dean, Julie Sawitzke, Paul N. Baird, Robyn H. Guymer, Dwight Stambolian, Anton Orlin, Johanna M. SeddonInga Peter, Alan F. Wright, Caroline Hayward, Andrew J. Lotery, Sarah Ennis, Michael B. Gorin, Daniel E. Weeks, Chia Ling Kuo, Aroon D. Hingorani, Reecha Sofat, Valentina Cipriani, Anand Swaroop, Mohammad Othman, Atsuhiro Kanda, Wei Chen, Goncalo R. Abecasis, John R. Yates, Andrew R. Webster, Anthony T. Moore, Johan H. Seland, Mati Rahu, Gisele Soubrane, Laura Tomazzoli, Fotis Topouzis, Jesus Vioque, Ian S. Young, Astrid E. Fletcher, Chris C. Patterson

Research output: Contribution to journalReview article

52 Scopus citations

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 (χ2 for trend = 14.9 (1 df); P = 0.0001), with a concomitant increase in the ε3 isoform (χ2 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.

Original languageEnglish (US)
Pages (from-to)1357-1364
Number of pages8
JournalAmerican journal of epidemiology
Volume173
Issue number12
DOIs
StatePublished - Jun 15 2011
Externally publishedYes

Keywords

  • aged
  • apolipoprotein E2
  • apolipoprotein E3
  • apolipoprotein E4
  • apolipoproteins E
  • longevity
  • meta-analysis
  • multicenter study

ASJC Scopus subject areas

  • Epidemiology

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  • Cite this

    McKay, G. J., Silvestri, G., Chakravarthy, U., Dasari, S., Fritsche, L. G., Weber, B. H., Keilhauer, C. N., Klein, M. L., Francis, P. J., Klaver, C. C., Vingerling, J. R., Ho, L., De Jong, P. T. D. V., Dean, M., Sawitzke, J., Baird, P. N., Guymer, R. H., Stambolian, D., Orlin, A., ... Patterson, C. C. (2011). Variations in apolipoprotein e frequency with age in a pooled analysis of a large group of older people. American journal of epidemiology, 173(12), 1357-1364. https://doi.org/10.1093/aje/kwr015