A novel cytochrome P-450IID6 mutant gene associated with Parkinson's disease.
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.
Tsuneoka
Y
Y
Department of Biochemistry, Kagawa Medical School.
Matsuo
Y
Y
Iwahashi
K
K
Takeuchi
H
H
Ichikawa
Y
Y
D001120:Arginine / Q000737:chemistry; D001483:Base Sequence; D003545:Cysteine / Q000737:chemistry; D019389:Cytochrome P-450 CYP2D6; D003577:Cytochrome P-450 Enzyme System / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D015252:Deoxyribonucleases, Type II Site-Specific; D005838:Genotype; D006720:Homozygote; D006801:Humans; D007564:Japan; D006899:Mixed Function Oxygenases / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D008969:Molecular Sequence Data; D009154:Mutation; D010300:Parkinson Disease / Q000201:enzymology / Q000235:genetics*; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length
D003577:Cytochrome P-450 Enzyme System; D001120:Arginine; D006899:Mixed Function Oxygenases; D019389:Cytochrome P-450 CYP2D6; D015252:Deoxyribonucleases, Type II Site-Specific; C037130:GCGC-specific type II deoxyribonucleases; D003545:Cysteine