Meta-analysis of the association between two neprilysin gene polymorphisms and Alzheimer's disease

Objective: The aim of this study is to evaluate the association between two neprilysin variants (rs989692 and rs3736187) and Alzheimer's disease (AD).

Methods: All eligible studies were searched in PubMed and Embase from inception to July 2014. Data was extracted by two investigators independently. The complete overdominant model (CC+TT vs. CT) and co-dominant model (GG vs. AA and GA vs. AA) were used for rs989692 and rs3736187, respectively. A comparison of allele frequencies was also conducted.

Results: Six studies containing 2555 AD patients and 1914 controls were included for rs989692 polymorphisms. The pooled odds ratio (OR) and confidence interval (CI) suggested that rs989692 polymorphisms were not associated with AD based on the current published studies (C vs. T, OR = 1.01, 95% CI = 0.85-1.19; CC+TT vs. CT, OR = 0.89, 95% CI = 0.78-1.01). Five studies containing 2438 AD patients and 1452 controls were identified for rs3736187 polymorphisms (G vs. A, OR = 0.77, 95% CI = 0.66-0.91; GG vs. AA, OR = 0.38, 95% CI = 0.19-0.77; GA vs. AA, OR = 0.81, 95% CI = 0.61-0.99). The result showed that rs3736187 polymorphisms were likely associated with the decreased risk of AD.

Conclusions: This meta-analysis indicates that rs3736187 (A/G) polymorphisms may be a potential beneficial single nucleotide polymorphism (SNP), which are associated with a decreased risk in AD. Further larger scale studies are necessary to validate gene-to-gene interactions and to define the association of neprilysin polymorphisms with AD.