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