@article{8115525f61694bd3804f6680bb12415a,
title = "Role of sepiapterin reductase gene at the PARK3 locus in Parkinson's disease",
abstract = "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.",
keywords = "PARK3, PD genetic studies, PD-GWAS, Parkinson disease, SPR",
author = "Manu Sharma and Maraganore, {Demetrius M.} and Ioannidis, {John P.A.} and Olaf Riess and Aasly, {Jan O.} and Grazia Annesi and Nadine Abahuni and Bentivoglio, {Anna Rita} and Alexis Brice and {Van Broeckhoven}, Christine and Chartier-Harlin, {Marie Christine} and Alain Dest{\'e}e and Ana Djarmati and Alexis Elbaz and Matthew Farrer and Carlo Ferrarese and Gibson, {J. Mark} and Suzana Gispert and Nobutaka Hattori and Barbara Jasinska-Myga and Christine Klein and Suzanne Lesage and Timothy Lynch and Peter Lichtner and Lambert, {Jean Charles} and Lang, {Anthony E.} and Mellick, {George D.} and {De Nigris}, Francesa and Grzegorz Opala and Aldo Quattrone and Chiara Riva and Ekaterina Rogaeva and Ross, {Owen A.} and Wataru Satake and Silburn, {Peter A.} and Jessie Theuns and Tatsushi Toda and Hiroyuki Tomiyama and Uitti, {Ryan J.} and Karin Wirdefeldt and Zbigniew Wszolek and Thomas Gasser and Rejko Kr{\"u}ger",
note = "Funding Information: USA: Demetrius M. Maraganore, M.D. (Department of Neurology, Mayo Clinic, Rochester, MN, USA), J. Eric Ahlskog, Ph.D., M.D. (Department of Neurology, Mayo Clinic, Rochester, MN, USA), Mariza de Andrade, Ph.D. (Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA), Timothy G. Lesnick, M.S. (Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA), and Walter A. Rocca, M.D., M.P.H. (Departments of Neurology and Health Sciences Research, Mayo Clinic, Rochester, MN, USA). Also, Harvey Checkoway, Ph.D. (Department of Environmental and Occupational Health Sciences, University of Washington, Seattle, WA, USA), Owen A. Ross, Ph.D. (Division of Neuroscience, Mayo Clinic, Jacksonville, FL, USA), Zbigniew K. Wszolek, M.D., and Ryan J. Uitti, M.D. (Department of Neurology, Mayo Clinic, Jacksonville, FL, USA). Funding: Z.K.W. is partially supported by the NIH/NINDS 1RC2NS070276, NS057567, P50NS072187, Mayo Clinic Florida (MCF) Research Committee CR programs (MCF #90052018 and MCF #90052030), and the gift from Carl Edward Bolch, Jr., and Susan Bass Bolch (MCF #90052031/PAU #90052). Funding Information: Japan: Nobutaka Hattori, M.D., Ph.D. (Department of Neurology, Juntendo University School of Medicine, Tokyo), Hiroyuki Tomiyama, M.D., Ph.D. (Department of Neurology, Juntendo University School of Medicine, Tokyo), Manabu Funayama, Ph.D. (Department of Neurology, and Research Institute for Diseases of Old Age, Graduate School of Medicine, Juntendo University, Tokyo), Hiroyo Yoshino, B.S. (Research Institute for Diseases of Old Age, Graduate School of Medicine, Juntendo University, Tokyo), Yuanzhe Li, M.D., Ph.D. (Department of Neurology, Juntendo University School of Medicine, Tokyo), Yoko Imamichi (Department of Neurology, Juntendo University School of Medicine, Tokyo), Tatsushi Toda, M.D. (Division of Neurology/Molecular Brain Science, Kobe University Graduate School of Medicine, Kobe, Japan), Wataru Satake (Division of Neurology/Molecular Brain Science, Kobe University Graduate School of Medicine, Kobe, Japan). Funding: This work was supported by a grant from the Japanese Ministry of Education, Culture, Sports, Science and Technology , Grants-in-Aid for Scientific Research (to HT: 21591098; to NH: 090052131), for Scientific Research on Priority Areas (to NH: 08071510), and for Young Scientists (to MF: 22790829). Funding Information: Funding to investigators was provided by the German Federal Ministry for Education and Research (BMBF, NGFNplus; 01GS08134) to T.G., O.R., and R.K., and Rapid Response Innovation Award from the Michael J. Fox Foundation to M.S.; Grants-in-Aid for Scientific Research (to HT: 21591098), and Grants-in-Aid from the Research Committee of CNS Degenerative Diseases and Perry syndrome (to HT: 22140901) from the Japanese Ministry of Education, Culture, Sports, Science and Technology . ",
year = "2011",
month = nov,
doi = "10.1016/j.neurobiolaging.2011.05.024",
language = "English",
volume = "32",
pages = "2108.e1--2108.e5",
journal = "Neurobiology of Aging",
issn = "0197-4580",
publisher = "Elsevier Inc.",
number = "11",
}