Evidence map›Paper›PMID 21332925›Full record

ArticleAging cell2011

Trade-off in the effects of the apolipoprotein E polymorphism on the ages at onset of CVD and cancer influences human lifespan.

Alexander M Kulminski, Irina Culminskaya, Svetlana V Ukraintseva, Konstantin G Arbeev, Liubov Arbeeva, Deqing Wu, Igor Akushevich, Kenneth C Land, Anatoli I Yashin

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In one paragraph

Article in Aging cell, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
35citing papers in PubMed, 2 pooled it
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

35 citing papers in PubMed, 2 syntheses or guidelines pooled it.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors.

Alexander M KulminskiCenter for Population Health and Aging, Duke University, Durham, NC 27708, USA. alexander.kulminski@duke.edu
Irina Culminskaya
Svetlana V Ukraintseva
Konstantin G Arbeev
Liubov Arbeeva
Deqing Wu
Igor Akushevich
Kenneth C Land
Anatoli I Yashin

Funding

EVALUATING NEW GENETIC EFFECTS ON HEALTH AND AGING FROM LONGITUDINAL DATAR01AG030612 · NIA · DUKE UNIVERSITY · PI YASHIN, ANATOLIY I · 2007 to 2011
$2.9M
NIA NIH HHS R01 AG030612NIA NIH HHS R01AG030612
6 · The paper itself

Abstract

Progress in unraveling the genetic origins of healthy aging is tempered, in part, by a lack of replication of effects, which is often considered a signature of false-positive findings. We convincingly demonstrate that the lack of genetic effects on an aging-related trait can be because of trade-offs in the gene action. We focus on the well-studied apolipoprotein E (APOE) e2/3/4 polymorphism and on lifespan and ages at onset of cardiovascular diseases (CVD) and cancer, using data on 3924 participants of the Framingham Heart Study Offspring cohort. Kaplan-Meier estimates show that the e4 allele carriers live shorter lives than the non-e4 allele carriers (log rank = 0.016). The adverse effect was attributed to the poor survival of the e4 homozygotes, whereas the effect of the common e3/4 genotype was insignificant. The e3/4 genotype, however, was antagonistically associated with onsets of those diseases predisposing to an earlier onset of CVD and a later onset of cancer compared to the non-e4 allele genotypes. This trade-off explains the lack of a significant effect of the e3/4 genotype on survival; adjustment for it in the Cox regression model makes the detrimental effect of the e4 allele highly significant (P = 0.002). This trade-off is likely caused by the lipid-metabolism-related (for CVD) and nonrelated (for cancer) mechanisms. An evolutionary rationale suggests that genetic trade-offs should not be an exception in studies of aging-related traits. Deeper insights into biological mechanisms mediating gene action are critical for understanding the genetic regulation of a healthy lifespan and for personalizing medical care.

Indexed as

Genetic Predisposition to DiseaseLongevityAdultAge of OnsetAllelesApolipoproteins ECardiovascular DiseasesCohort StudiesGene FrequencyGenetic Association StudiesGenotypeHumansKaplan-Meier EstimateLipidsNeoplasmsPolymorphism, GeneticApolipoproteins ELipidsProtein Isoforms

Identifiers

PMID21332925
PMCPMC3094490

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.