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The role of lipid-related genes, aging-related processes, and environment in healthspan.

Publication ,  Journal Article
Kulminski, AM; Culminskaya, I; Arbeev, KG; Ukraintseva, SV; Stallard, E; Arbeeva, L; Yashin, AI
Published in: Aging cell
April 2013

The inherent complexity of aging-related traits can temper progress in unraveling the genetic origins of healthspan. We focus on two generations in the Framingham Heart Study, the original (FHS) and offspring (FHSO) cohorts, to determine whether aging-related processes in changing environments can substantially impact the role of lipid-related genes discovered in candidate gene (the apolipoprotein E (APOE) e2/3/4 polymorphism) and genome-wide (the APOB rs1042034 (C/T)) studies, in regulation of total cholesterol (TC) and onset of cardiovascular disease (CVD). We demonstrate that the APOE e4 allele and APOB CC genotype can play detrimental, neutral, and protective sex-specific roles in the etiology of CVD at different ages and in different environments. We document antagonistic roles for the e4 allele in the onset of CVD characterized by detrimental effects at younger ages (RR≤ 75 years = 1.49, P = 7.5 × 10(-4) ) and protective effects at older ages (RR76+years = 0.77, P = 0.044) for FHS participants. We found that disregarding the role of aging erroneously nullifies the significant effects of the e4 allele in this sample (RR = 0.92, P = 0.387). The leading biogenetic pathways mediating genetic effects on CVD may be more relevant to lipid metabolism for APOB than APOE. Aging-related processes can modulate the strength of genetic associations with TC in the same individuals at different chronological ages. We found substantial differences in the effects of the same APOE and APOB alleles on CVD and TC across generations. The results suggest that aging-related processes in changing environments may play key roles in the genetics of healthspan. Detailed systemic integrative analyses may substantially advance the progress.

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Published In

Aging cell

DOI

EISSN

1474-9726

ISSN

1474-9718

Publication Date

April 2013

Volume

12

Issue

2

Start / End Page

237 / 246

Related Subject Headings

  • Polymorphism, Genetic
  • Middle Aged
  • Male
  • Longevity
  • Lipid Metabolism
  • Humans
  • Genotype
  • Gene-Environment Interaction
  • Gene Frequency
  • Female
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Kulminski, A. M., Culminskaya, I., Arbeev, K. G., Ukraintseva, S. V., Stallard, E., Arbeeva, L., & Yashin, A. I. (2013). The role of lipid-related genes, aging-related processes, and environment in healthspan. Aging Cell, 12(2), 237–246. https://doi.org/10.1111/acel.12046
Kulminski, Alexander M., Irina Culminskaya, Konstantin G. Arbeev, Svetlana V. Ukraintseva, Eric Stallard, Liubov Arbeeva, and Anatoli I. Yashin. “The role of lipid-related genes, aging-related processes, and environment in healthspan.Aging Cell 12, no. 2 (April 2013): 237–46. https://doi.org/10.1111/acel.12046.
Kulminski AM, Culminskaya I, Arbeev KG, Ukraintseva SV, Stallard E, Arbeeva L, et al. The role of lipid-related genes, aging-related processes, and environment in healthspan. Aging cell. 2013 Apr;12(2):237–46.
Kulminski, Alexander M., et al. “The role of lipid-related genes, aging-related processes, and environment in healthspan.Aging Cell, vol. 12, no. 2, Apr. 2013, pp. 237–46. Epmc, doi:10.1111/acel.12046.
Kulminski AM, Culminskaya I, Arbeev KG, Ukraintseva SV, Stallard E, Arbeeva L, Yashin AI. The role of lipid-related genes, aging-related processes, and environment in healthspan. Aging cell. 2013 Apr;12(2):237–246.
Journal cover image

Published In

Aging cell

DOI

EISSN

1474-9726

ISSN

1474-9718

Publication Date

April 2013

Volume

12

Issue

2

Start / End Page

237 / 246

Related Subject Headings

  • Polymorphism, Genetic
  • Middle Aged
  • Male
  • Longevity
  • Lipid Metabolism
  • Humans
  • Genotype
  • Gene-Environment Interaction
  • Gene Frequency
  • Female