No or only population-specific effect of PON1 on human longevity: A comprehensive meta-analysis
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- 作者：Amke Caliebe ; Rabea Kleindorp ; Hé ; lè ; ne Blanché ; Lene Christiansen ; Annibale Aless ; ro Puca ; Irene Maeve Rea ; Eline Slagboom ; Friederike Flachsbart ; Kaare Christensen ; Gerald Rimbach ; Stef
- 关键词：Genetic association study ; Paraoxonase 1 ; Ageing ; Long-lived individuals ; APOE interaction
- 刊名：Ageing Research Reviews
- 出版年：2010
- 出版时间：July 2010
- 年：2010
- 卷：9
- 期：3
- 页码：238-244
- 全文大小：325 K
文摘
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 4 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).