No or only population-specific effect of PON1 on human longevity: A comprehensive meta-analysis

被引：21

作者：

Caliebe, Amke ^{[2
]}

Kleindorp, Rabea ^{[1
]}

Blanche, Helene ^{[3
]}

Christiansen, Lene ^{[4
]}

Puca, Annibale Alessandro ^{[5
,6
]}

Rea, Irene Maeve ^{[7
]}

Slagboom, Eline ^{[8
]}

Flachsbart, Friederike ^{[1
]}

Christensen, Kaare ^{[9
]}

Rimbach, Gerald ^{[10
]}

Schreiber, Stefan ^{[1
]}

Nebel, Almut ^{[1
]}

机构：

[1] Univ Kiel, Inst Clin Mol Biol, Kiel, Germany

[2] Univ Kiel, Inst Med Informat & Stat, Kiel, Germany

[3] Fdn Jean Dausset CEPH, Paris, France

[4] Univ So Denmark, Inst Publ Hlth, Odense, Denmark

[5] CNR, Ist Tecnol Biomed, Segrate, Italy

[6] IRCCS Multimed, Milan, Italy

[7] Queens Univ Belfast, Sch Med Dent & Biomed Sci, Belfast BT7 1NN, Antrim, North Ireland

[8] Leiden Univ, Med Ctr, Mol Epidemiol Sect, NL-2300 RA Leiden, Netherlands

[9] Univ So Denmark, Danish Ageing Res Ctr, Odense, Denmark

[10] Univ Kiel, Inst Human Nutr & Food Sci, Kiel, Germany

来源：

AGEING RESEARCH REVIEWS | 2010年 / 9卷 / 03期

关键词：

Genetic association study; Paraoxonase; 1; Ageing; Long-lived individuals; APOE interaction; CORONARY-ARTERY-DISEASE; PARAOXONASE ACTIVITY; OXIDATIVE STRESS; ASSOCIATION ANALYSIS; GENETIC ASSOCIATION; ALZHEIMERS-DISEASE; ELDERLY SUBJECTS; HEART-DISEASE; RISK; GENOTYPE;

D O I：

10.1016/j.arr.2010.03.003

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

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 QJR 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 epsilon 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). (C) 2010 Elsevier Ireland Ltd. All rights reserved.

引用

页码：238 / 244

页数：7

共 54 条

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