CYP2D6*4 allele polymorphism increases the risk of Parkinson's disease: evidence from meta-analysis

Many epidemiological studies have been conducted to explore the association between a single CYP2D6 gene polymorphism and Parkinson's disease (PD) susceptibility. However, the results remain controversial.

To clarify the effects of a single CYP2D6 gene polymorphism on the risk of PD, a meta-analysis of all available studies relating to CYP2D6*4 polymorphism and the risk of PD was conducted.

A comprehensive literature search of PubMed, EMBASE, and the China National Knowledge Infrastructure (CNKI) up to September 1, 2013 was conducted. Data were extracted by two independent authors and pooled odds ratio (OR) with 95% confidence interval (CI) were calculated. Meta-regression, Galbraith plots, subgroup analysis, sensitivity analysis, and publication bias analysis were also performed.

Twenty-two separate comparisons consisting of 2,629 patients and 3,601 controls were included in our meta-analysis. The pooled analyses showed a significant association between CYP2D6*4G/A polymorphism and PD risk in all of the comparisons (A vs. G allele: OR = 1.28, 95% CI = 1.14-1.43, P = 0.001; AA vs. GG: OR = 1.43, 95% CI = 1.06-1.93, P = 0.018; AG vs. GG: OR = 1.22, 95% CI = 1.06-1.40, P = 0.006; AG+AA vs. GG: OR = 1.26, 95% CI = 1.10-1.44, P = 0.001; AA vs. AG+GG: OR = 1.37, 95% CI = 1.02-1.83, P = 0.036). In subgroup analysis stratified by ethnicity, significant associations were also demonstrated in Caucasians but not in Asians. No significant association was found in subgroup analysis stratified by age of onset or disease form.

We concluded that the CYP2D6*4G/A polymorphism denotes an increased genetic susceptibility to PD in the overall population, especially in Caucasians. Further large and well-designed studies are needed to confirm this association.