title: No or only population-specific effect of PON1 on human longevity: a comprehensive meta-analysis.
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).
authors.affiliation: Institute of Medical Informatics and Statistics, Christian-Albrechts-University, Kiel, Germany.
authors.forename: Amke
authors.initials: A
authors.lastname: Caliebe
authors.forename: Rabea
authors.initials: R
authors.lastname: Kleindorp
authors.forename: Hélène
authors.initials: H
authors.lastname: Blanché
authors.forename: Lene
authors.initials: L
authors.lastname: Christiansen
authors.forename: Annibale Alessandro
authors.initials: AA
authors.lastname: Puca
authors.forename: Irene Maeve
authors.initials: IM
authors.lastname: Rea
authors.forename: Eline
authors.initials: E
authors.lastname: Slagboom
authors.forename: Friederike
authors.initials: F
authors.lastname: Flachsbart
authors.forename: Kaare
authors.initials: K
authors.lastname: Christensen
authors.forename: Gerald
authors.initials: G
authors.lastname: Rimbach
authors.forename: Stefan
authors.initials: S
authors.lastname: Schreiber
authors.forename: Almut
authors.initials: A
authors.lastname: Nebel
mesh_terms: D053327:Apolipoprotein E4 / Q000097:blood; D043303:Aryldialkylphosphatase / Q000235:genetics*; D005060:Europe; D006801:Humans; D008136:Longevity / Q000235:genetics*; D014481:United States
chemical_list: D053327:Apolipoprotein E4; D043303:Aryldialkylphosphatase; C468406:PON1 protein, human