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Trade-offs in the effects of the apolipoprotein E polymorphism on risks of diseases of the heart, cancer, and neurodegenerative disorders: insights on mechanisms from the Long Life Family Study.

Publication ,  Journal Article
Kulminski, AM; Arbeev, KG; Culminskaya, I; Ukraintseva, SV; Stallard, E; Province, MA; Yashin, AI
Published in: Rejuvenation research
April 2015

The lack of evolutionary established mechanisms linking genes to age-related traits makes the problem of genetic susceptibility to health span inherently complex. One complicating factor is genetic trade-off. Here we focused on long-living participants of the Long Life Family Study (LLFS), their offspring, and spouses to: (1) Elucidate whether trade-offs in the effect of the apolipoprotein E e4 allele documented in the Framingham Heart Study (FHS) are a more general phenomenon, and (2) explore potential mechanisms generating age- and gender-specific trade-offs in the effect of the e4 allele on cancer, diseases of the heart, and neurodegenerative disorders assessed retrospectively in the LLFS populations. The e4 allele can diminish risks of cancer and diseases of the heart and confer risks of diseases of the heart in a sex-, age-, and LLFS-population-specific manner. A protective effect against cancer is seen in older long-living men and, potentially, their sons (>75 years, relative risk [RR]>75=0.48, p=0.086), which resembles our findings in the FHS. The protective effect against diseases of the heart is limited to long-living older men (RR>76=0.50, p=0.016), as well. A detrimental effect against diseases of the heart is characteristic for a normal LLFS population of male spouses and is specific for myocardial infarction (RR=3.07, p=2.1×10(-3)). These trade-offs are likely associated with two inherently different mechanisms, including disease-specific (detrimental; characteristic for a normal male population) and systemic, aging-related (protective; characteristic for older long-living men) mechanisms. The e4 allele confers risks of neurological disorders in men and women (RR=1.98, p=0.046). The results highlight the complex role of the e4 allele in genetic susceptibility to health span.

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Published In

Rejuvenation research

DOI

EISSN

1557-8577

ISSN

1549-1684

Publication Date

April 2015

Volume

18

Issue

2

Start / End Page

128 / 135

Related Subject Headings

  • United States
  • Sex Factors
  • Risk Factors
  • Risk Assessment
  • Protective Factors
  • Proportional Hazards Models
  • Polymorphism, Genetic
  • Pedigree
  • Odds Ratio
  • Neurodegenerative Diseases
 

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Kulminski, A. M., Arbeev, K. G., Culminskaya, I., Ukraintseva, S. V., Stallard, E., Province, M. A., & Yashin, A. I. (2015). Trade-offs in the effects of the apolipoprotein E polymorphism on risks of diseases of the heart, cancer, and neurodegenerative disorders: insights on mechanisms from the Long Life Family Study. Rejuvenation Research, 18(2), 128–135. https://doi.org/10.1089/rej.2014.1616
Kulminski, Alexander M., Konstantin G. Arbeev, Irina Culminskaya, Svetlana V. Ukraintseva, Eric Stallard, Michael A. Province, and Anatoli I. Yashin. “Trade-offs in the effects of the apolipoprotein E polymorphism on risks of diseases of the heart, cancer, and neurodegenerative disorders: insights on mechanisms from the Long Life Family Study.Rejuvenation Research 18, no. 2 (April 2015): 128–35. https://doi.org/10.1089/rej.2014.1616.
Kulminski AM, Arbeev KG, Culminskaya I, Ukraintseva SV, Stallard E, Province MA, et al. Trade-offs in the effects of the apolipoprotein E polymorphism on risks of diseases of the heart, cancer, and neurodegenerative disorders: insights on mechanisms from the Long Life Family Study. Rejuvenation research. 2015 Apr;18(2):128–35.
Kulminski, Alexander M., et al. “Trade-offs in the effects of the apolipoprotein E polymorphism on risks of diseases of the heart, cancer, and neurodegenerative disorders: insights on mechanisms from the Long Life Family Study.Rejuvenation Research, vol. 18, no. 2, Apr. 2015, pp. 128–35. Epmc, doi:10.1089/rej.2014.1616.
Kulminski AM, Arbeev KG, Culminskaya I, Ukraintseva SV, Stallard E, Province MA, Yashin AI. Trade-offs in the effects of the apolipoprotein E polymorphism on risks of diseases of the heart, cancer, and neurodegenerative disorders: insights on mechanisms from the Long Life Family Study. Rejuvenation research. 2015 Apr;18(2):128–135.
Journal cover image

Published In

Rejuvenation research

DOI

EISSN

1557-8577

ISSN

1549-1684

Publication Date

April 2015

Volume

18

Issue

2

Start / End Page

128 / 135

Related Subject Headings

  • United States
  • Sex Factors
  • Risk Factors
  • Risk Assessment
  • Protective Factors
  • Proportional Hazards Models
  • Polymorphism, Genetic
  • Pedigree
  • Odds Ratio
  • Neurodegenerative Diseases