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Int J Mol Epidemiol Genet 2013;4(1):61-69
Original Article
Genotype and age at Parkinson disease diagnosis
Susan Searles Nielsen, Theo K Bammler, Lisa G Gallagher, Federico M Farin, WT Longstreth Jr, Gary M Franklin, Phillip D
Swanson, Harvey Checkoway
University of Washington, Department of Environmental and Occupational Health Sciences, Seattle, WA, USA; University of
Washington, Department of Neurology, Seattle, WA, USA; University of Washington, Department of Epidemiology, Seattle, WA,
USA
Received December 22, 2012; Accepted January 30, 2013; Epub March 18, 2013; Published March 28, 2013
Abstract: 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. (IJMEG1212006).
Keywords: Arachidonic acid, CYP2J2 protein, CYP3A7 protein, divalent metal transporter-1, GSTM5 protein, idiopathic
Parkinson disease, linoleic acid, SLC11A2 protein
Address correspondence to: Susan Searles Nielsen, University of Washington, Department of Environmental and
Occupational Health Sciences, Box 357234, Seattle, WA 98195-7234. Phone: 206-685-2487; Fax: 206-685-3990; E-mail:
ssn@u.washington.edu
Original Article
Genotype and age at Parkinson disease diagnosis
Susan Searles Nielsen, Theo K Bammler, Lisa G Gallagher, Federico M Farin, WT Longstreth Jr, Gary M Franklin, Phillip D
Swanson, Harvey Checkoway
University of Washington, Department of Environmental and Occupational Health Sciences, Seattle, WA, USA; University of
Washington, Department of Neurology, Seattle, WA, USA; University of Washington, Department of Epidemiology, Seattle, WA,
USA
Received December 22, 2012; Accepted January 30, 2013; Epub March 18, 2013; Published March 28, 2013
Abstract: 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. (IJMEG1212006).
Keywords: Arachidonic acid, CYP2J2 protein, CYP3A7 protein, divalent metal transporter-1, GSTM5 protein, idiopathic
Parkinson disease, linoleic acid, SLC11A2 protein
Address correspondence to: Susan Searles Nielsen, University of Washington, Department of Environmental and
Occupational Health Sciences, Box 357234, Seattle, WA 98195-7234. Phone: 206-685-2487; Fax: 206-685-3990; E-mail:
ssn@u.washington.edu
