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 643AD cases and 1375 controls were included for CYP2D64 polymorphism, and 4 studies consisted of 411AD cases and 603 controls were included for CYP2D6 phenotypes. With respect to CYP2D64 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.