Review, comparison and meta-analysis of CYP2D6 polymorphism and association with Parkinson’s disease in Caucasian and Asian populations

Daniel Kam Yin Chan, Dennis Cordato, Wai Tak Hung

    Research output: Chapter in Book / Conference PaperChapter

    Abstract

    Despite the recent advances in the discovery of a synuclein gene and parkin gene which help to elucidate the pathogenesis of hereditary Parkinson's disease in some families, the aetiology of Parkinson's disease remains unclear in the majority of the sporadic onset cases. Both environmental and genetic risk factors are thought to be involved and these factors are thought to interact in causing Parkinson's disease. The hypothesis that failure to metabolise xenobiotics is a putative risk factor in predisposed individuals with susceptible genetic defects remain an attractive possibility. This hypothesis is further supported by some drug addicts who developed parkinsonism after self-administrating synthetic meperidine analogues contaminated with 1-methyl-4-phenyl-1 ,2,3,6-tetrahydropyridine. This paper reviews and compares the evidence in literature of the cytochrome P450 2D6 (CYP2D6 debrisoquine 4-hydroxylase) genetic polymorphism in Caucasian and Asian populations and the association with Parkinson's disease. Furthermore, it also attempts to clarify the issue by using meta-analyses for analysing the results of genotypic studies of CYP2D6 and Parkinson's disease in the two populations. Interestingly, this latest and largest meta-analysis showed that there is a weak association of CYP2D6 poor metaboliser genotype and Parkinson 's disease in Caucasians (Odds ratio 1.3; 95% CI: 1.04 - 1.63). However, the situation is less clear in Asians as the poor metaboliser genotype is very rare and meta-analysis of heterozygotes in Asians carrying one mutant gene (instead of two) indicated an increased risk of2.07 (95% CI 1.33 - 3.24) compared to controls. However, the results of poor metaboliser genotypes in Caucasians and heterozygotes in Asians are clouded by the fact that there is significant heterogeneity amongst the studies used in the meta-analyses. Therefore, although the meta-analysis did overcome the sample size problems of allele association studies, other limitations remain including the lack of consideration of environmental factors, lack of consideration of interactions, diagnostic accuracy for Parkinson's disease and consideration of multiple genes being involved.
    Original languageEnglish
    Title of host publicationFocus on Parkinson's Disease Research
    EditorsMarianne J. Willow
    Place of PublicationU.S.A.
    PublisherNova
    Pages1-19
    Number of pages19
    ISBN (Print)1594549249
    Publication statusPublished - 2006

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