PON1 is a longevity gene: Results of a meta-analysis

Paraoxonase 1 (PON1) is one of the most studied genes regarding cardiovascular risk, oxidative stress and inflammation. Several lines of evidence suggests that PON1 promotes an atheroprotective effect. Patients carrying PON1 codon 192 QQ genotype display a higher risk of cardiovascular events, the major cause of mortality in the elderly: it can be predicted that gene variants increasing the risk of mortality will be under-represented in long-living individuals. We first reported that PON1 R allele (R+) carriers are significantly more represented in Italian centenarians; subsequently this topic has been addressed by many other groups, and here we report a meta-analysis on 11 studies in different populations selected by a review of the literature available in PubMed and testing the effect of the Q192R polymorphism on human ageing. QUORUM guidelines for meta-analysis have been followed, and a total number of 5962 subjects have been included: 2795 young controls (<65 years of age) and 3167 old subjects (>65 years of age). The Mantel-Haenszel weighting for pooling in presence of a fixed effects model has been applied. The meta-analysis of R carriers showed a significant result with an overall OR of 1.16 (1.04-1.30, 95% CI, p=0.006). The meta-analysis of QR genotype also showed a significant result, with an overall OR of 1.14 (1.02-1.27, 95% CI, p=0.016). The results show that PON1 gene variants at codon 192 impact on the probability of attaining longevity, and that subjects carrying RR and QR genotypes (R+ carriers) are favoured in reaching extreme ages. These results likely represent the counterpart of the effects observed on cardiovascular diseases (CVD), as centenarians and nonagenarians escaped or delayed the onset of the major age-related diseases, including CVD.