Association between the oxidative polymorphism and early onset of Parkinson's disease

Clin Pharmacol Ther. 1995 Mar;57(3):291-8. doi: 10.1016/0009-9236(95)90154-X.

Abstract

The frequency of five cytochrome P450IID6 allelic variants was studied in deoxyribonucleic acid from 123 patients with Parkinson's disease and 150 healthy volunteers. This was achieved by the use of mutation-specific polymerase chain reaction and restriction fragment length polymorphism. The analyses of the CYP2D6 genotype revealed no evidence for a higher prevalence of poor metabolizers among patients with Parkinson's disease. However, increased frequency of patients with Parkinson's disease with the genotype CYP2D6wt/CYP2D6B was observed. This is attributable exclusively to subjects with early onset of the disease (28 to 49 years), with a relative risk ratio of 4.16 (95% confidence limits, 2.0 to 8.3; p < 0.0005). The subjects who had late-onset Parkinson's disease (> or = 50 years) had genotypes and CYP2D6 allele frequencies similar to the healthy subjects. This indicates that the oxidative polymorphism is related to early-onset but not to late-onset Parkinson's disease. A different influence of CYP2D6 genotype on the risk of development of Parkinson's disease is observed in Spaniards, compared with previous findings in British subjects. These results suggest the combined effect of environmental toxins and CYP2D6 in the cause of Parkinson's disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Age of Onset
  • Alleles
  • Cytochrome P-450 CYP2D6
  • Cytochrome P-450 Enzyme System / genetics*
  • Female
  • Genotype
  • Humans
  • Male
  • Middle Aged
  • Mixed Function Oxygenases / genetics*
  • Oxidation-Reduction
  • Parkinson Disease / enzymology*
  • Parkinson Disease / ethnology
  • Parkinson Disease / genetics*
  • Polymerase Chain Reaction
  • Polymorphism, Restriction Fragment Length
  • Risk
  • Spain

Substances

  • Cytochrome P-450 Enzyme System
  • Mixed Function Oxygenases
  • Cytochrome P-450 CYP2D6