Genotype and age at Parkinson disease diagnosis.

Parkinson disease (PD) is a degenerative movement disorder that results from the destruction of dopaminergic neurons in the midbrain substantia nigra. Both genetic and environmental factors contribute to PD risk, and likely to age at diagnosis. Among 258 newly diagnosed non-Hispanic Caucasian cases from Group Health Cooperative in western Washington State, we assessed whether diagnosis age was associated with 1,327 single nucleotide polymorphisms in genes related to central nervous system function, oxidative stress, inflammation or metal transport. We conducted linear regression to assess the age difference per variant allele while adjusting for sex and smoking. Of the polymorphisms associated with PD diagnosis age (ptrend<0.05), three demonstrated similar associations among 64 PD cases from the University of Washington Neurology Clinic, were not similarly associated (pinteraction<0.05) with age in general among 436 unrelated non-Hispanic Caucasian controls from the source population, and were predicted to be functional according to a public National Institute of Environmental Health Sciences polymorphism database. The most robust association was for rs10889162, a polymorphism in a predicted transcription factor binding site -582 bp from CYP2J2 arachidonic acid epoxygenase. Each variant allele was associated with 5.04 years older diagnosis age (95% confidence interval 2.28-7.80, p=0.0003). This association did not vary by sex or smoking history. Polymorphisms in predicted microRNA binding sites in GSTM5 and SLC11A2 were also associated with >2-year differences in diagnosis age. These results await confirmation in other series of incident cases, but suggest that selected genes and environmental exposures may influence PD diagnosis age.