Mitochondrial NADH dehydrogenase and CYP2D6 genotypes in Lewy-body parkinsonism.

摘要: The cause of nerve-cell death in sporadic Parkinson's disease remains unknown. Although environmental factors have been traditionally implicated the etiology disease, recent studies strongly suggest that there is a genetic contribution to this multifactorial disorder. We studied archival brain tissue from clinically and neuropathologically verified cases using nonradioactive cycle sequencing restriction enzymatic analysis polymerase chain reaction products. Twenty-one Parkinsonian brains with stem Lewy-bodies 77 control were genotyped at two mitochondrial loci previously neurodegenerative disease. In addition, genotyping was performed for alleles debrisoquine 4-hydroxylase gene (CYP2D6). A heteroplasmic mtDNAG5460A missense mutation ND2 subunit NADH dehydrogenase three times more frequent Parkinson (4/21) compared controls (5/77). homoplasmic mtDNAA4336G transition which alters tRNAGln product found one case. Frequencies CYP2D6G1934A CYP2D6C2938T not significantly different between controls. Two high degrees heteroplasmy ND2G5460A homozygous case showed very numbers substantia nigra. results study are line concept may be involved susceptibility. They provide hint ND2(5460) mutation, combination other factors, could play role pathogenesis subset patients.