CYP2D6*4 Allele Polymorphism Increases the Risk of Parkinson’s Disease: Evidence from Meta-Analysis

Abstract

BackgroundMany 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.ObjectivesTo 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.MethodsA 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.ResultsTwenty-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.ConclusionsWe 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.

Role of CYP2E1 polymorphisms in breast cancer: a systematic review and meta-analysis

“…The predefined criteria, which cover the credibility of controls, the representativeness of cases, specimens of cases when determining genotypes, Hardy–Weinberg equilibrium in controls, and total sample size, was structured as a 16-item list with scores ranging from 0 to 15 by Qin et al [19]. and has been quoted by several meta-analyses [20, 21] (see Additional file 1: Table S1). As done previously, the studies with scores ≥10 were defined as high-quality studies, while the rest were low-quality studies.…”

Alternative Splicing in the Cytochrome P450 Superfamily Expands Protein Diversity to Augment Gene Function and Redirect Human Drug Metabolism

“…However, the complex etiology of these disorders can make it difficult to interpret the exact role that a P450 SNP might play in the actual onset or progression of a disease. Multiple studies of various intergenic, intronic, and exonic polymorphisms that alter human drug and xenobiotic metabolism have also been reported (CYP1A1, Allorge et al, 2003;CYP2C19, de Morais et al, 1994;Ibeanu et al, 1999;Satyanarayana et al, 2009;Sun et al, 2015;CYP2D6, Toscano et al, 2006;Lu et al, 2013;Wang et al, 2014;CYP3A4, Elens et al, 2011;and CYP3A5, Kuehl et al, 2001;Busi and Cresteil, 2005;Lee et al, 2007;García-Roca et al, 2012). In many cases, the most pharmacologically relevant SNPs are those affecting the innate splicing behavior of a given gene.…”

Tipping Points and Endogenous Determinants of Nigrostriatal Degeneration by MPTP

“…An alternative activation pathway, MPTP conversion by cytochrome P-450 2D6 (CYP2D6), was also suggested [42,43]. Indeed, genetic association studies revealed a link between a polymorphism at the locus CYP2D6 and PD susceptibility [44]. However, biochemical activity studies indicated that high CYP2D6 activities were correlated with a diminished risk of PD [45,46].…”