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

Abstract

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 CYP2D6*4 polymorphism, and 4 studies consisted of 411AD 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.

• Authors: Yu Lu, Xue Qin, Shan Li, Xiaolian Zhang, Yu He, Qiliu Peng, Yan Deng, Jian Wang, Li Xie, Taijie Li, Zhiyu Zeng
• Journal: Journal of the neurological sciences (J Neurol Sci) Vol. 343 Issue 1-2 Pg. 15-22 (Aug 15 2014) ISSN: 1878-5883 [Electronic] Netherlands
• PMID: 24909950 (Publication Type: Journal Article, Meta-Analysis)
• Copyright: Copyright © 2014 Elsevier B.V. All rights reserved.

Chemical References

• Cytochrome P-450 CYP2D6

Topics

• Alzheimer Disease (ethnology, genetics)
• Cytochrome P-450 CYP2D6 (genetics)
• Databases, Factual (statistics & numerical data)
• Genetic Association Studies (statistics & numerical data)
• Genetic Predisposition to Disease
• Humans
• Polymorphism, Single Nucleotide (genetics)
• Risk Factors
• White People