Association Study of Parkin Gene Polymorphisms With Idiopathic Parkinson Disease

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Abstract
PARKINSON DISEASE (PD) is the second most common human neurodegenerative disorder and is typically characterized by resting tremor, bradykinesia, and rigidity. The incidence and prevalence of PD increase with age, and thus, as the current population ages, the number of patients with PD will increase. Parkinson disease is a complex disease thought to result from the interaction of environmental and genetic factors. We completed a genomic screening of patients with idiopathic PD collected from 13 collaborating centers and found evidence in support of linkage to several genomic regions.1 Overall, there was little evidence for linkage on chromosome 6. However, when families were stratified by age at onset (AAO), significant evidence for linkage with a microsatellite lying in the Parkin gene (logarithm of odds score, 5.47 at marker D6S305) was detected in 18 families, each containing at least one individual with an AAO younger than 40 years. Parkin is an E2-dependent ubiquitin protein ligase known to carry pathogenic mutations in patients with autosomal recessive juvenile parkinsonism, but its role in idiopathic PD is still being explored. Subsequent analysis revealed the presence of 9 different Parkin mutations in 5% of our overall PD sample.2 We define mutations as genetic variants severe enough to cause an alteration of the protein function. Mutations are observed in affected individuals and possibly in their siblings but not in the general population.