Quantitative assessment of CYP2D6 polymorphisms and risk of Alzheimer's disease: A meta-analysis

Background: CYP2D6 gene encoding CYP2D6 enzyme belonging to the cytochrome P450 system has aroused long attention being a candidate gene for Alzheimer's disease (AD), but the results remain inconsistent and underpowered. Objectives: To investigate the contradictory results, the effect of single CYP2D6 polymorphism- CYP2D6*4, together with CYP2D6 phenotypes on the risk of AD, was evaluated using a meta-analysis. Methods: Electronic database search of PubMed, Embase and Cochrane Library was conducted up to Apr 17, 2014. Odds ratio (OR) along with the 95% confidence interval (CI) was calculated. Subgroup analysis was performed to examine the impact of CYP2D6 variants on different ethnic. Meta-regression was performed to explore possible source of heterogeneity. Results: A total of 11 studies involving 643 AD cases and 1375 controls were included for CYP2D6*4 polymorphism, and 4 studies consisted of 411 AD cases and 603 controls were included for CYP2D6 phenotypes. With respect to CYP2D6*4 polymorphism, significantly increased risk of AD was found in allelic contrast model of A vs. G (OR = 1.29, 95%CI = 1.03-1.62, P = 0.026), co-dominant genetic model AA vs. GG (OR = 1.91, 95%CI = 1.04-3.51, P = 0.038); and recessive genetic model AA vs. AG + GG (OR = 1.88, 95%CI = 1.03-3.46, P = 0.041) in the overall populations. Similar results were also indicated in subgroup analysis in Caucasians. As for CYP2D6 phenotypes, no significant association with AD was revealed. Conclusions: Our data support that the CYP2D6*4 polymorphism but not CYP2D6 phenotypes might be associated with increased AD risk, particularly in Caucasian populations. (C) 2014 Elseviet B.V. All rights reserved.