Genetic analysis of the CYP2D6 gene in patients with Parkinson's disease

Metabolism: Clinical and Experimental
Y TsuneokaY Watanabe

Abstract

To further investigate the association between Parkinson's disease (PD) and genetic polymorphism of the CYP2D6 gene, a mutant allele (CVP2D6J) frequently observed in the Japanese population and related to EM/PM polymorphism (phenotypically, individuals are either extensive metabolizers [EM] or poor metabolizers [PM] of debrisoquine) was investigated. The CYP2D6J gene with a nucleotide substitution from C to T at position 188 (the HphI site in exon 1), which reduces CYP2D6 enzyme activity, was analyzed by polymerase chain reaction (PCR) and by digestion with HphI. No significant relationship was observed between PD patients and controls for this mutation. This suggests that the EM/PM polymorphism of CYP2D6 contributes little to the pathogenesis of PD. To further study the molecular basis for the relationship between PD and CYP2D6, the heterogeneity of CYP2D6 was investigated by combined genotype analysis of the two mutant CYP2D6 genes (ie, CYP2D6J, the HphI site mutation in exon 1, and CYP2D6L, the HhaI site mutation in exon 6). Although some characteristic patterns of the combined genotypes were observed in both PD patients and controls, a strong association between the heterogeneity of the CYP2D6 gene and PD was not shown by c...Continue Reading

Citations

Nov 11, 1998·Journal of the American Geriatrics Society·E Gómez-TortosaB T Hyman
May 13, 1999·Annals of Neurology·M WangY Mizuno

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