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

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22 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 epsilon4 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)238-44
Number of pages7
JournalAgeing research reviews
Volume9
Issue number3
DOIs
Publication statusPublished - Jul 2010

Bibliographical note

2010 Elsevier Ireland Ltd. All rights reserved.

ASJC Scopus subject areas

  • Ageing
  • Biochemistry
  • Biotechnology
  • Molecular Biology
  • Neurology

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    Caliebe, A., Kleindorp, R., Blanché, H., Christiansen, L., Puca, A. A., Rea, I. M., 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, 9(3), 238-44. https://doi.org/10.1016/j.arr.2010.03.003