Role of sepiapterin reductase gene at the PARK3 locus in Parkinson's disease

No Thumbnail Available
File version
Sharma, Manu
Maraganore, Demetrius M
Ioannidis, John PA
Riess, Olaf
Aasly, Jan O
Annesi, Grazia
Abahuni, Nadine
Bentivoglio, Anna Rita
Brice, Alexis
Van Broeckhoven, Christine
Chartier-Harlin, Marie-Christine
Destee, Alain
Djarmati, Ana
Elbaz, Alexis
Farrer, Matthew
Ferrarese, Carlo
Gibson, J Mark
Gispert, Suzana
Hattori, Nobutaka
Jasinska-Myga, Barbara
Klein, Christine
Lesage, Suzanne
Lynch, Timothy
Lichtner, Peter
Lambert, Jean-Charles
Lang, Anthony E
Mellick, George D
De Nigris, Francesa
Opala, Grzegorz
Quattrone, Aldo
Riva, Chiara
Rogaeva, Ekaterina
Ross, Owen A
Satake, Wataru
Silburn, Peter A
Theuns, Jessie
Toda, Tatsushi
Tomiyama, Hiroyuki
Uitti, Ryan J
Wirdefeldt, Karin
Wszolek, Zbigniew
Gasser, Thomas
Krueger, Rejko
Griffith University Author(s)
Primary Supervisor
Other Supervisors
File type(s)

Sepiapterin reductase (SPR) gene is an enzyme which catalyses the final step of tetrahydrobiopterin synthesis (BH4) and was implicated in Parkinson's disease (PD) pathogenesis as a candidate gene for PARK3 locus. A number of studies yielded association of the PARK3 locus with PD, and SPR knockout mice were shown to display parkinsonian features. To evaluate the role of SPR gene polymorphisms in diverse populations in PD, we performed collaborative analyses in the Genetic Epidemiology of Parkinson Disease (GEO-PD) Consortium. A total of 5 single nucleotide polymorphisms (3 in the promoter region and 2 in the 3′ untranslated region [UTR]) were genotyped. Fixed as well as random effect models were used to provide summary risk estimates of SPR variants. A total of 19 sites provided data for 6547 cases and 9321 controls. Overall odds ratio estimates varied from 0.92 to 1.01. No overall association with the SPR gene using either fixed effect or random effect model was observed in the studied population. I2 Metric varied from 0% to 36.2%. There was some evidence for an association for participants of North European/Scandinavian descent with the strongest signal for rs1876487 (odds ratio = 0.82; p value = 0.003). Interestingly, families which were used to map the PARK3 locus, have Scandinavian ancestry suggesting a founder effect. In conclusion, this large association study for the SPR gene revealed no association for PD worldwide. However, taking the initial mapping of the PARK3 into account, the role of a population-specific effect warrants consideration in future studies.

Journal Title

Neurobiology of Aging

Conference Title
Book Title




Thesis Type
Degree Program
Publisher link
Patent number
Grant identifier(s)
Rights Statement
Rights Statement
Item Access Status
Access the data
Related item(s)

Clinical sciences


Neurology and neuromuscular diseases

Persistent link to this record