Paraoxonase (PON1) polymorphisms Q192R and L55M are not associated with human longevity: A meta-analysis.

Abstract

Genetic mutations in the paraoxonase 1 (PON1) encoding gene have been considered to affect mortality and of these the functional promoter region polymorphisms Q192R and L55M are among the most widely studied. The aim of this study was to determine whether the Q192R and L55M polymorphisms of PON1 can increase susceptibility to longevity. A meta-analysis was performed to obtain a comprehensive estimation of the association between Q192R and L55M and longevity in long-lived individuals (LLIs) aged 80 years or more. A search was carried out in the PubMed database (from January 2001 to May 2014) to obtain data on the role of PON1 polymorphisms in longevity and a pooled odds ratio (OR) with a 95% confidence interval (CI) was used to assess the associations. The meta-analysis was based on 9 studies of PON1 Q192R and 5 studies of PON1 L55M that covered a total of 5086 LLIs and 4494 controls. Overall, significantly increased risks were not observed for either Q192R or L55M. The results of the statistical calculations were as follows: R vs. Q (additive model): OR = 1.080, 95% CI = 0.989-1.179, p = 0.088 and RR + RQ vs. QQ (dominant model): OR = 1.099, 95% CI = 0.975-1.240, p = 0.124; M vs. L (additive model): OR = 0.946, 95% CI = 0.862-1.039, p = 0.245 and MM + ML vs. LL (dominant model): OR = 0.951, 95% CI = 0.836-1.081, p = 0.442 for Q192R and L55M, respectively. The results did not change with an age cut-off among the LLIs of ≥ 93 years. No evidence that the Q192R and L55M polymorphisms of PON1 impacted on the probability of reaching extreme ages was found although this cannot be completely ruled out; however, the possibility of population-specific effects due to the influence of and interaction between different genes or environmental factors could not be ruled out.