| Article ID | Journal | Published Year | Pages | File Type |
|---|---|---|---|---|
| 1913460 | Journal of the Neurological Sciences | 2014 | 8 Pages |
•CYP2D6*4 polymorphism plays a role in the pathogenesis of Alzheimer's disease.•CYP2D6*4 polymorphism in Caucasians may associate with an increased AD risk.•CYP2D6 phenotypes were not associated with increased Alzheimer's disease risk.
BackgroundCYP2D6 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.ObjectivesTo 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.MethodsElectronic 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.ResultsA 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.ConclusionsOur data support that the CYP2D6*4 polymorphism but not CYP2D6 phenotypes might be associated with increased AD risk, particularly in Caucasian populations.
