Abstract
Genetic polymorphism of the CYP2D6 gene [phenotypically individuals are either poor metabolizers (PM) or extensive metabolizers (EM)] has been reported to be associated with susceptibility to Parkinson's disease. We analyzed CYP2D6 genes from Japanese patients and controls, and found that EM/PM polymorphism is not a suitable marker for populations with a low PM frequency. However, a novel mutant highly associated with Parkinson's disease was discovered. The mutation was located at the HhaI site in exon 6 and changed a conserved amino acid residue, Arg296, to Cys296. The risk factor for the mutant homozygote was 5.56 (95% CI, 1.30-23.82). These results suggest that the HhaI polymorphism in the CYP2D6 gene is a part of the molecular basis of Parkinson's disease.
MeSH terms
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Arginine / chemistry
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Base Sequence
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Cysteine / chemistry
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Cytochrome P-450 CYP2D6
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Cytochrome P-450 Enzyme System / chemistry
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Cytochrome P-450 Enzyme System / genetics*
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Cytochrome P-450 Enzyme System / metabolism
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Deoxyribonucleases, Type II Site-Specific
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Genotype
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Homozygote
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Humans
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Japan
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Mixed Function Oxygenases / chemistry
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Mixed Function Oxygenases / genetics*
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Mixed Function Oxygenases / metabolism
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Molecular Sequence Data
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Mutation
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Parkinson Disease / enzymology
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Parkinson Disease / genetics*
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Polymerase Chain Reaction
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Polymorphism, Restriction Fragment Length
Substances
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Cytochrome P-450 Enzyme System
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Arginine
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Mixed Function Oxygenases
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Cytochrome P-450 CYP2D6
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Deoxyribonucleases, Type II Site-Specific
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GCGC-specific type II deoxyribonucleases
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Cysteine