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 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 journalArticle

47 Citations (Scopus)

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

Fingerprint

Apolipoproteins
Apolipoproteins E
Protein Isoforms
Macular Degeneration
Genes
Apolipoprotein E4
Homozygote
Case-Control Studies
Cohort Studies
Smoking
Genotype
Population

Keywords

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

ASJC Scopus subject areas

  • Epidemiology

Cite this

McKay, G. J., Silvestri, G., Chakravarthy, U., Dasari, S., Fritsche, L. G., Weber, B. H., ... 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

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

In: American Journal of Epidemiology, Vol. 173, No. 12, 15.06.2011, p. 1357-1364.

Research output: Contribution to journalArticle

McKay, GJ, Silvestri, G, Chakravarthy, U, Dasari, S, Fritsche, LG, Weber, BH, Keilhauer, CN, Klein, M, Francis, PJ, Klaver, CC, Vingerling, JR, Ho, L, De Jong, PTDV, Dean, M, Sawitzke, J, Baird, PN, Guymer, RH, Stambolian, D, Orlin, A, Seddon, JM, Peter, I, Wright, AF, Hayward, C, Lotery, AJ, Ennis, S, Gorin, MB, Weeks, DE, Kuo, CL, Hingorani, AD, Sofat, R, Cipriani, V, Swaroop, A, Othman, M, Kanda, A, Chen, W, Abecasis, GR, Yates, JR, Webster, AR, Moore, AT, Seland, JH, Rahu, M, Soubrane, G, Tomazzoli, L, Topouzis, F, Vioque, J, Young, IS, Fletcher, AE & Patterson, CC 2011, 'Variations in apolipoprotein e frequency with age in a pooled analysis of a large group of older people', American Journal of Epidemiology, vol. 173, no. 12, pp. 1357-1364. https://doi.org/10.1093/aje/kwr015
McKay GJ, Silvestri G, Chakravarthy U, Dasari S, Fritsche LG, Weber BH et al. Variations in apolipoprotein e frequency with age in a pooled analysis of a large group of older people. American Journal of Epidemiology. 2011 Jun 15;173(12):1357-1364. https://doi.org/10.1093/aje/kwr015
McKay, Gareth J. ; Silvestri, Giuliana ; Chakravarthy, Usha ; Dasari, Shilpa ; Fritsche, Lars G. ; Weber, Bernhard H. ; Keilhauer, Claudia N. ; Klein, Michael ; Francis, Peter J. ; Klaver, Caroline C. ; Vingerling, Johannes R. ; Ho, Lintje ; De Jong, Paulus T D V ; Dean, Michael ; Sawitzke, Julie ; Baird, Paul N. ; Guymer, Robyn H. ; Stambolian, Dwight ; Orlin, Anton ; Seddon, Johanna M. ; Peter, Inga ; Wright, Alan F. ; Hayward, Caroline ; Lotery, Andrew J. ; Ennis, Sarah ; Gorin, Michael B. ; Weeks, Daniel E. ; Kuo, Chia Ling ; Hingorani, Aroon D. ; Sofat, Reecha ; Cipriani, Valentina ; Swaroop, Anand ; Othman, Mohammad ; Kanda, Atsuhiro ; Chen, Wei ; Abecasis, Goncalo R. ; Yates, John R. ; Webster, Andrew R. ; Moore, Anthony T. ; Seland, Johan H. ; Rahu, Mati ; Soubrane, Gisele ; Tomazzoli, Laura ; Topouzis, Fotis ; Vioque, Jesus ; Young, Ian S. ; Fletcher, Astrid E. ; Patterson, Chris C. / Variations in apolipoprotein e frequency with age in a pooled analysis of a large group of older people. In: American Journal of Epidemiology. 2011 ; Vol. 173, No. 12. pp. 1357-1364.
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AU - Silvestri, Giuliana

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AU - Dasari, Shilpa

AU - Fritsche, Lars G.

AU - Weber, Bernhard H.

AU - Keilhauer, Claudia N.

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AU - Vingerling, Johannes R.

AU - Ho, Lintje

AU - De Jong, Paulus T D V

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AU - Guymer, Robyn H.

AU - Stambolian, Dwight

AU - Orlin, Anton

AU - Seddon, Johanna M.

AU - Peter, Inga

AU - Wright, Alan F.

AU - Hayward, Caroline

AU - Lotery, Andrew J.

AU - Ennis, Sarah

AU - Gorin, Michael B.

AU - Weeks, Daniel E.

AU - Kuo, Chia Ling

AU - Hingorani, Aroon D.

AU - Sofat, Reecha

AU - Cipriani, Valentina

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AU - Othman, Mohammad

AU - Kanda, Atsuhiro

AU - Chen, Wei

AU - Abecasis, Goncalo R.

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AU - Webster, Andrew R.

AU - Moore, Anthony T.

AU - Seland, Johan H.

AU - Rahu, Mati

AU - Soubrane, Gisele

AU - Tomazzoli, Laura

AU - Topouzis, Fotis

AU - Vioque, Jesus

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AU - Fletcher, Astrid E.

AU - Patterson, Chris C.

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KW - apolipoprotein E3

KW - apolipoprotein E4

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KW - longevity

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