No or only population-specific effect of PON1 on human longevity: A comprehensive meta-analysis

Amke Caliebe, Rabea Kleindorp, Hélène Blanché, Lene Christiansen, Annibale Alessandro Puca, Irene Maeve Rea, Eline Slagboom, Friederike Flachsbart, Kaare Christensen, Gerald Rimbach, Stefan Schreiber, Almut Nebel

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

Paraoxonase 1 (PON1) has been suggested as a plausible candidate gene for human longevity due to its modulation of cardiovascular disease risk, by preventing oxidation of atherogenic low-density lipoprotein. The role of the PON1 192 Q/R polymorphism has been analyzed for association with survival at old age in several populations, albeit with controversial results. To reconcile the conflicting evidence, we performed a large association study with two samples of 2357 Germans and 1025 French, respectively. We combined our results with those from seven previous studies in the largest and most comprehensive meta-analysis on PON1 192 Q/R and longevity to-date, to include a total of 9580 individuals. No significant association of PON1 192 Q/R with longevity was observed, for either R allele or carriership. This finding relied on very large sample sizes, is supported by different analysis methods and is therefore considered very robust. Moreover, we have investigated a potential interaction of PON1 192 Q/R with APOE ε4 using data from four populations. Whereas a significant result was found in the German sample, this could not be confirmed in the other examined groups. Our large-scale meta-analysis provided no evidence that the PON1 192 Q/R polymorphism is associated with longevity, but this does not exclude the possibility of population-specific effects due to the influence of, and interaction between, different genetic and/or environmental factors (e.g. diet).

Original languageEnglish
Pages (from-to)238-244
Number of pages7
JournalAgeing Research Reviews
Volume9
Issue number3
DOIs
Publication statusPublished - Jul 2010

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Aryldialkylphosphatase
Meta-Analysis
Population
Association reactions
Polymorphism
Nutrition
LDL Lipoproteins
Sample Size
human PON1 protein
Cardiovascular Diseases
Genes
Alleles
Modulation
Diet
Oxidation
Survival

Keywords

  • Ageing
  • APOE interaction
  • Genetic association study
  • Long-lived individuals
  • Paraoxonase 1

ASJC Scopus subject areas

  • Ageing
  • Biochemistry
  • Biotechnology
  • Molecular Biology
  • Neurology

Cite this

No or only population-specific effect of PON1 on human longevity : A comprehensive meta-analysis. / Caliebe, Amke; Kleindorp, Rabea; Blanché, Hélène; Christiansen, Lene; Puca, Annibale Alessandro; Rea, Irene Maeve; Slagboom, Eline; Flachsbart, Friederike; Christensen, Kaare; Rimbach, Gerald; Schreiber, Stefan; Nebel, Almut.

In: Ageing Research Reviews, Vol. 9, No. 3, 07.2010, p. 238-244.

Research output: Contribution to journalArticle

Caliebe, A, Kleindorp, R, Blanché, H, Christiansen, L, Puca, AA, Rea, IM, Slagboom, E, Flachsbart, F, Christensen, K, Rimbach, G, Schreiber, S & Nebel, A 2010, 'No or only population-specific effect of PON1 on human longevity: A comprehensive meta-analysis', Ageing Research Reviews, vol. 9, no. 3, pp. 238-244. https://doi.org/10.1016/j.arr.2010.03.003
Caliebe, Amke ; Kleindorp, Rabea ; Blanché, Hélène ; Christiansen, Lene ; Puca, Annibale Alessandro ; Rea, Irene Maeve ; Slagboom, Eline ; Flachsbart, Friederike ; Christensen, Kaare ; Rimbach, Gerald ; Schreiber, Stefan ; Nebel, Almut. / No or only population-specific effect of PON1 on human longevity : A comprehensive meta-analysis. In: Ageing Research Reviews. 2010 ; Vol. 9, No. 3. pp. 238-244.
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