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Candidate genes and Parkinson's disease: where to next?

The etiology of PD remains unknown. For several decades, environmental factors were thought to be primarily responsible for disease pathogenesis. However, in recent years, the identification of mutations in three different genes (α-synuclein,1 parkin,2 and ubiquitin C-terminal hydrolase3) and two different loci (2p134 and 4p5) underscored the importance of genetic factors in at least some cases of parkinsonism. These mutations still appear relatively rare because they have not yet been found in sporadic PD, with the possible exception of the Greek population.6 This apparent lack of monogenic causes of sporadic PD has led investigators to undertake association studies for polymorphisms in candidate genes in an attempt to identify susceptibility genes or risk factors for developing PD. The results have been conflicting.7-8 Two studies published in …