TY - JOUR
T1 - No or only population-specific effect of PON1 on human longevity: A comprehensive meta-analysis
AU - Caliebe, Amke
AU - Kleindorp, Rabea
AU - Blanché, Hélène
AU - Christiansen, Lene
AU - Puca, Annibale Alessandro
AU - Rea, Irene Maeve
AU - Slagboom, Eline
AU - Flachsbart, Friederike
AU - Christensen, Kaare
AU - Rimbach, Gerald
AU - Schreiber, Stefan
AU - Nebel, Almut
N1 - 2010 Elsevier Ireland Ltd. All rights reserved.
PY - 2010/7
Y1 - 2010/7
N2 - 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).
AB - 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).
UR - http://www.scopus.com/inward/record.url?scp=77952544536&partnerID=8YFLogxK
U2 - 10.1016/j.arr.2010.03.003
DO - 10.1016/j.arr.2010.03.003
M3 - Article
C2 - 20362697
VL - 9
SP - 238
EP - 244
JO - Ageing Research Reviews
JF - Ageing Research Reviews
IS - 3
ER -