Authors: Caliebe A; Kleindorp R; Blanché H; Christiansen L; Puca AA; Rea IM; Slagboom E; Flachsbart F; Christensen K; Rimbach G; Schreiber S; Nebel A

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).

Keywords: Apolipoprotein E4/blood; Aryldialkylphosphatase/*genetics; Europe; Humans; Longevity/*genetics; United States
Journal: Ageing research reviews
Volume: 9
Issue: 3
Pages: 238-44
Date: April 7, 2010
PMID: 20362697
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Citation:

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 9: 238-44.


Longevity Variant Associations (p-value):
  • rs662 (0.086)
  • rs662 (0.33)
  • rs662 (0.11)
  • rs662 (0.55)

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