[Genetics and environmental factors of Parkinson disease]

Abstract

We present a review on the genetic and environmental factors implicated in the aetiology of Parkinson's disease. The environmental hypothesis was strongly suggested about 20 years ago after the report of a parkinsonian syndrome in young adults that were intoxicated by a neurotoxin called MPTP which selectively destroys nigrostriatal dopaminergic neurons. Several chemical products used in herbicides and pesticides are similar structurally to MPTP, including paraquat, diquat and rotenone. Epidemiological studies have revealed an increased risk for Parkinson's disease with the use of pesticides and herbicides or the consumption of well water in rural areas of industrialised countries. However, it has not been possible to identify any causative environmental chemical agent in the aetiology of Parkinson's disease despite intensive research. Comparatively, the genetic hypothesis of Parkinson's disease has gained considerable interest during the last decade. Epidemiological studies reveal a family history in 10-25 p. 100 Parkinson's disease patients. Several large kindreds with autosomal dominant Parkinson's disease associated with mutations of alpha-synuclein gene (PARK 1) were recently described. alpha-synuclein is a constituant of Lewy bodies, the hallmark of idiopathic Parkinson's disease. However, alpha-synuclein gene mutations are rare as opposed to parkin gene mutations (PARK 2), which are frequently found in autosomal recessive and sporadic young onset Parkinson's disease patients. Other genes or locus are implicated in autosomal dominant familial cases (PARK 3, 4 and 5). Nevertheless, a pure genetic origin can be demonstrated only in a minority of Parkinson's disease patients. Investigation of the possible interaction between genes and environment and of several candidate genes gave contradictory results, notably concerning the association between allelic variants of CYP2D6 gene and the occurrence of Parkinson's disease. In conclusion, the aetiology of Parkinson's disease remains unknown. There are probably several types or causes of Parkinson's disease. In most cases, this heterogeneity could be attributed both to genetic and environmental factors.