The nitric oxide synthase 3 G894T polymorphism associated with Alzheimer's disease risk: a meta-analysis.

Shengyuan Liu,Changyi Wang,Fangfang Zeng,Bin Zhao,Zhongwei Chen,Keshen Li

doi:10.1038/srep13598

Abstract

The association between the G894T polymorphism (Glu298Asp) of nitric oxide synthase 3 (NOS3) and risk of Alzheimer’s disease (AD) was explored by performing a meta-analysis of case-control studies. Bibliographical searches were conducted in the MEDLINE, EMBASE, and China National Knowledge Infrastructure (CNKI) databases without any language limitations. Two investigators independently assessed abstracts for relevant studies, and reviewed all eligible studies. We adopted regrouping in accordance with the most probably appropriate genetic model. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of this association. We performed a meta-analysis including 21 published articles with 23 case-control studies (5,670 cases and 5,046 controls). In the analyses, we found significant association between G894T polymorphism and AD risk under a complete overdominant model (GG + TT vs. GT) (OR = 1.18; 95%CI, 1.04–1.35; P = 0.010). When stratified by time of AD onset, we found the association between this polymorphism and AD susceptibility to be more substantial among late onset patients than among early onset patients (OR for late vs. early onset: 1.33 vs. 1.02, P interaction = 0.049). The meta-analysis showed that the polymorphism G894T of NOS3 was associated with risk of AD.

Highlights

Alzheimer’s disease (AD), called senile dementia of the Alzheimer type or primary degenerative dementia of the Alzheimer’s type, is a degenerative disease of the central nervous system characterized by a gradual decline in memory and cognition, which has been correlated with synaptic dysfunction and loss, and eventually to neuronal death[1]
We conducted a meta-analysis of the existing epidemiologic studies by using a comprehensive search strategy to determine whether there was an association between G894T polymorphism of nitric oxide synthase 3 (NOS3) and risk of AD
Case-control studies from 21 publications[2,6,7,8,21,22,23,24,25,26,27,28,29,30,31,32,33,34,35,36,37] including 5,670 cases and 5,046 controls were used to evaluate the association of G894T polymorphism with AD risk (Table 1)

Summary

Material and Methods

We conducted a systematically electronic search using the following terms “(Alzheimer* or AD) and (NOS* or nitric oxide synthase*) and (polymorphism* or genotype* or variant*)” in the PubMed database (from 1966 to May, 2015). The following information was collected in a predefined data collection form: the first author’s name, year of publication, country of origin, ethnicity, AD diagnosis method, source of controls, proportion of men in cases and controls, total number of cases and controls, mean (range) age of cases and controls, time of AD onset, and number of cases and controls with different genotypes. We performed subgroup analysis according to time of AD onset, APOE ε4 polymorphism, ethnicity, HWE in controls, control population source, year of publication, and quality score, respectively. 0.2 was set as an FPRP threshold and assigned a prior probability of 0.1 to detect an odds ratio (OR) of 0.67/1.50 (protective/risk effects) for an association with genotypes under investigation. All statistical analyses were completed using Stata Version 11.0 (College Station, TX, USA)

Results

Discussion

Summary