Genetic susceptibility and the occurrence of Parkinson's disease.
A genetic cause of Parkinson's disease is supported by the occurrence of familial disease with identified gene defects, a increased prevalence in homozygous twin pairs and the existence of family clusters. However, familial Parkinson's disease is an interesting but rare form of the disorder and twin studies indicate that heredity may be one of the factors which contribute to the onset of Parkinson's disease. Similarly, the increased risk of Parkinson's disease in relatives of an affected individual suggests a genetic contribution, but alone this is unlikely to explain the onset of nigral cell degeneration. To account for apparently sporadic cases of Parkinson's disease, an involvement of susceptibility genes has been proposed to explain the inherited component of the disorder. However, to date most studies have failed to identify specific genotypic associations with Parkinson's disease. For example, despite extensive investigation no clear association is known between cytochrome P450 isoenzymes, specifically CYP2D6, and Parkinson's disease. Indeed, a genetic component may not be required to explain sporadic Parkinson's disease since environmental factors are associated with an increased prevalence of the illness and the actions of specific toxins are known to induce nigral cell degeneration. In addition, endogenous toxin formation in the brain leads to a variety of processes which may initiate nigral cell death in Parkinson's disease. However, in all probability both genetic and environmental or toxic components contribute to the occurrence of Parkinson's disease and it is likely that an interaction between these factors results in nigral cell degeneration.
Jenner
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Neurodegenerative Diseases Research Centre, Division of Pharmacology & Therapeutics, Guy's, King's and St. Thomas' School of Biomedical Sciences, King's College, London SW3 6LX, UK.