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

Manu Sharma; Demetrius M. Maraganore; John P.A. Ioannidis; Olaf Riess; Jan O. Aasly; Grazia Annesi; Nadine Abahuni; Anna Rita Bentivoglio; Alexis Brice; Christine Van Broeckhoven; Marie Christine Chartier-Harlin; Alain Destée; Ana Djarmati; Alexis Elbaz; Matthew Farrer; Carlo Ferrarese; J. Mark Gibson; Suzana Gispert; Nobutaka Hattori; Barbara Jasinska-Myga; Christine Klein; Suzanne Lesage; Timothy Lynch; Peter Lichtner; Jean Charles Lambert; Anthony E. Lang; George D. Mellick; Francesa De Nigris; Grzegorz Opala; Aldo Quattrone; Chiara Riva; Ekaterina Rogaeva; Owen A. Ross; Wataru Satake; Peter A. Silburn; Jessie Theuns; Tatsushi Toda; Hiroyuki Tomiyama; Ryan J. Uitti; Karin Wirdefeldt; Zbigniew Wszolek; Thomas Gasser; Rejko Krüger

doi:10.1016/j.neurobiolaging.2011.05.024

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

Manu Sharma^*, Demetrius M. Maraganore, John P.A. Ioannidis, Olaf Riess, Jan O. Aasly, Grazia Annesi, Nadine Abahuni, Anna Rita Bentivoglio, Alexis Brice, Christine Van Broeckhoven, Marie Christine Chartier-Harlin, Alain Destée, Ana Djarmati, Alexis Elbaz, Matthew Farrer, Carlo Ferrarese, J. Mark Gibson, Suzana Gispert, Nobutaka Hattori, Barbara Jasinska-MygaChristine Klein, Suzanne Lesage, Timothy Lynch, Peter Lichtner, Jean Charles Lambert, Anthony E. Lang, George D. Mellick, Francesa De Nigris, Grzegorz Opala, Aldo Quattrone, Chiara Riva, Ekaterina Rogaeva, Owen A. Ross, Wataru Satake, Peter A. Silburn, Jessie Theuns, Tatsushi Toda, Hiroyuki Tomiyama, Ryan J. Uitti, Karin Wirdefeldt, Zbigniew Wszolek, Thomas Gasser, Rejko Krüger

^*Korrespondierende/r Autor/-in für diese Arbeit

Institut für Neurogenetik

25 Zitate (Scopus)

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. I ² 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.

Originalsprache	Englisch
Zeitschrift	Neurobiology of Aging
Jahrgang	32
Ausgabenummer	11
ISSN	0197-4580
DOIs	https://doi.org/10.1016/j.neurobiolaging.2011.05.024
Publikationsstatus	Veröffentlicht - 01.11.2011

Fördermittel

Australia: From the Queensland Parkinson's Project: R.S. Boyle and A. Sellbach (Princess Alexandra Hospital, Brisbane), J.D. O'Sullivan (Royal Brisbane and Women's Hospital, Brisbane), G.T. Sutherland, G.A. Siebert and N.N.W. Dissanayaka (Eskitis Institute for Cell and Molecular Therapies, Griffith University, Nathan, QLD). Belgium: Christine Van Broeckhoven, Ph.D., D.Sc. (Neurodegenerative Brain Diseases Group, Department of Molecular Genetics, VIB; and Laboratory of Neurogenetics, Institute Born-Bunge, University of Antwerp; Antwerpen), Jessie Theuns, PhD (Neurodegenerative Brain Diseases Group, Department of Molecular Genetics, VIB; and Laboratory of Neurogenetics, Institute Born-Bunge, University of Antwerp; Antwerpen), David Crosiers, M.D. (Neurodegenerative Brain Diseases Group, Department of Molecular Genetics, VIB; and Laboratory of Neurobiology, Institute Born-Bunge, University of Antwerp; and Department of Neurology, University Hospital Antwerp; Antwerpen), Barbara Pickut, M.D. (Department of Neurology, University Hospital Antwerp; Antwerpen), Sebastiaan Engelborghs, M.D., Ph.D. (Laboratory of Neurochemistry and Behavior, Institute Born-Bunge, University of Antwerp; and Department of Neurology and Memory Clinic, Hospital Network Antwerp Middelheim and Hoge Beuken; Antwerpen), Bram Meeus (Neurodegenerative Brain Diseases Group, Department of Molecular Genetics, VIB; and Laboratory of Neurogenetics, Institute Born-Bunge, University of Antwerp; Antwerpen), Peter P. De Deyn, M.D., Ph.D. (Laboratory of Neurochemistry and Behavior, Institute Born-Bunge, University of Antwerp; and Department of Neurology and Memory Clinic, Hospital Network Antwerp Middelheim and Hoge Beuken; Antwerpen), Patrick Cras, M.D., Ph.D. (Laboratory of Neurobiology, Institute Born-Bunge, University of Antwerp; and Department of Neurology, University Hospital Antwerp; Antwerpen). Funding: The research at this site was in part supported by the Special Research Fund of the University of Antwerp, the Medical Research Foundation Antwerp and Neurosearch, the Research Foundation Flanders (FWO), the Flanders government agency for Innovation by Science and Technology (IWT), the Foundation for Alzheimer Research (SAO/FRMA), the Belgian Science Policy Office Interuniversity Attraction Poles (IAP) Program P6/43, a Methusalem Excellence Grant of the Flanders Government and, and the Alzheimer’s Association USA,. B.M. received a Ph.D. fellowship of the IWT and D.C. of the FWO; J.T. received a FWO postdoctoral fellowship. Canada: Ekaterina Rogaeva, Ph.D. (Tanz Centre for Research in Neurodegenerative Diseases, Department of Medicine, Division of Neurology, University of Toronto, ON, Canada); Anthony E. Lang, M.D., Movement Disorders Centre, Toronto Western Hospital, University of Toronto, Toronto, ON, Canada. France: From the French Parkinson's Disease Genetics Study Group: Y. Agid, M. Anheim, A.-M. Bonnet, M. Borg, A. Brice, E. Broussolle, J.C. Corvol, P. Damier, A. Destée, A. Dürr, F. Durif, S. Lesage, E. Lohmann, P. Pollak, O. Rascol, F. Tison, C. Tranchant, F. Viallet, and M. Vidailhet. Also, Christophe Tzourio (Inserm U708, Paris), Philippe Amouyel (Inserm U744, Lille), Marie-Anne Loriot (Inserm UMRS775, Paris). Eugénie Mutez (Inserm UMR837, Service de Neurologie et de Pathologie du Mouvement CHRU de Lille, University Lille Nord de France), Aurélie Duflot, (UMR837 Inserm-University Lille 2, CHRU de Lille), Jean-Philippe Legendre (Service de Neurologie et Pathologie du Mouvement, Clinique de Neurologie du CHU de Lille), Nawal Waucquier (Service de Neurologie et Pathologie du Mouvement, Clinique de Neurologie du CHU de Lille), the 2 Centres de Ressources Biologiques (IPL-Lille, CHRU-Lille) and its scientific committee (AD, MCCH, P. Amouyel, F. Pasquier, R. Bordet). Funding: This work is supported by the French National Agency of Research (ANR-08-MNP-012). Lille: Financial support from CHRU de Lille, University Lille 2, Inserm, French Ministry PHRCs (1994/, 2002/1918, 2005/1914), Association France Parkinson (2005), Fondation de France 2004-013306, Fondation de la Recherche Médicale (2006), P.P.F. (Synucléothèque 2005-2009), Germany: Thomas Gasser, M.D., (Department of Neurology, University Hospital Tuebingen), Olaf Riess, M.D. (Department of Neurology, University Hospital Tuebingen), Daniela Berg, M.D., (Department of Neurology, University Hospital Tuebingen), Claudia Schulte, M.Sc. (Department of Neurology, University Hospital Tuebingen), Christine Klein, M.D. (Section of Clinical and Molecular Neurogenetics at the Department of Neurology, University of Lübeck), Ana Djarmati, Ph.D. (Department of Neurology, University of Lübeck), Johann Hagenah, M.D. (Department of Neurology, University of Lübeck), Katja Lohmann, Ph.D. (Section of Clinical and Molecular Neurogenetics at the Department of Neurology, University of Lübeck), Georg Auburger, M.D. (Department of Neurology, Goethe University Frankfurt am Main, Germany), Rüdiger Hilker, M.D. (Department of Neurology, Goethe University Frankfurt am Main, Germany), Simone van de Loo, M.D. (Department of Neurology, Goethe University Frankfurt am Main, Germany). Greece: Efthimios Dardiotis, M.D. (Department of Neurology, Faculty of Medicine, University of Thessaly and Institute of Biomedical Research & Technology, CERETETH, Larissa), Vaia Tsimourtou (Department of Neurology, Faculty of Medicine, University of Thessaly, Larissa), Styliani Ralli (Department of Neurology, Faculty of Medicine, University of Thessaly, Larissa), Persa Kountra, M.D. (Department of Neurology, Faculty of Medicine, University of Thessaly, Larissa), Konstantinos Aggelakis (Institute of Biomedical Research & Technology, CERETETH, Larissa). 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). Ireland: Prof. Tim Lynch, FRCPI, FRCP (The Dublin Neurological Institute at the Mater Misericordiae University Hospital, Clinical Investigator at the Conway Institute, University College Dublin, Ireland), and Dr J. Mark Gibson, M.D. (Department of Neurology, Royal Victoria Hospital, Belfast, Ireland). Italy: Enza Maria Valente, M.D., Ph.D. (IRCCS, Casa Sollievo della Sofferenza Hospital, Mendel Institute, San Giovanni Rotondo), Alessandro Ferraris, M.D., (IRCCS, Casa Sollievo della Sofferenza Hospital, Mendel Institute, San Giovanni Rotondo), Bruno Dallapiccola (Mendel Institute, Casa Sollievo della Sofferenza Hospital, Rome), Tamara Ialongo, M.D., Ph.D. (Institute of Neurology, Catholic University, Rome), Laura Brighina, M.D., Ph.D. (Department of Neurology, Ospedale San Gerarado, Monza, Italy), Barbara Corradi, Ph.D. (Department of Paediatrics, University of Milano-Bicocca, Monza), Roberto Piolti, M.D. (Department of Neurology, Ospedale San Gerardo, Monza, Italy), Patrizia Tarantino, Ph.D. (Institute of Neurological Sciences, National Research Council), and Ferdinanda Annesi, Ph.D. (Institute of Neurological Sciences, National Research Council). Norway: J. Aasly, M.D. (Department of Neurology, University of Trondheim, Norway). Poland: Grzegorz Opala, M.D., Ph.D. (Department of Neurology, Aging, Degenerative and Cerebrovascular Disorders, Medical University of Silesia, Katowice), Barbara Jasinska-Myga, M.D., Ph.D. (Department of Neurology, Aging, Degenerative and Cerebrovascular Disorders, Medical University of Silesia, Katowice), Gabriela Klodowska-Duda, M.D., Ph.D. (Department of Neurology, Aging, Degenerative and Cerebrovascular Disorders, Medical University of Silesia, Katowice), Magdalena Boczarska-Jedynak, M.D., Ph.D. (Department of Neurology, Aging, Degenerative and Cerebrovascular Disorders, Medical University of Silesia, Katowice). Singapore: Eng King Tan, M.D., Ph.D. (National Medical and Biomedical Research Councils, and the Duke-NUS Graduate Medical School, Singapore Millenium Foundation). Sweden: Andrea Carmine Belin, Ph.D. (Department of Neuroscience, Karolinska Institutet, Stockholm), Lars Olson, Professor (Department of Neuroscience, Karolinska Institutet, Stockholm), Dagmar Galter, Ph.D. (Department of Neuroscience, Karolinska Institutet, Stockholm), Marie Westerlund, Ph.D. (Department of Neuroscience, Karolinska Institutet, Stockholm), Olof Sydow, Ph.D., (Department of Clinical Neuroscience, Karolinska University Hospital, Stockholm). Also Christer Nilsson, M.D., Ph.D. (Department of Geriatric Psychiatry, Lund University), Andreas Puschmann, M.D. (Department of Neurology, Lund University Hospital, Department of Geriatric Psychiatry, Lund University). Taiwan: J.J. Lin, M.D., Department of Neurology, Cushang Show-Chwan Hospital, Taiwan. 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 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 . Appendix: A

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10.1016/j.neurobiolaging.2011.05.024

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Sharma, M., Maraganore, D. M., Ioannidis, J. P. A., Riess, O., Aasly, J. O., Annesi, G., Abahuni, N., Bentivoglio, A. R., Brice, A., Van Broeckhoven, C., Chartier-Harlin, M. C., Destée, A., Djarmati, A., Elbaz, A., Farrer, M., Ferrarese, C., Gibson, J. M., Gispert, S., Hattori, N., ... Krüger, R. (2011). Role of sepiapterin reductase gene at the PARK3 locus in Parkinson's disease. Neurobiology of Aging, 32(11). https://doi.org/10.1016/j.neurobiolaging.2011.05.024

@article{7cf5219e1ccd497b9594a657866eaafe,

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. I 2 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.",

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",

year = "2011",

month = nov,

day = "1",

doi = "10.1016/j.neurobiolaging.2011.05.024",

language = "English",

volume = "32",

journal = "Neurobiology of Aging",

issn = "0197-4580",

publisher = "Elsevier Inc.",

number = "11",

}

Sharma, M, Maraganore, DM, Ioannidis, JPA, Riess, O, Aasly, JO, Annesi, G, Abahuni, N, Bentivoglio, AR, Brice, A, Van Broeckhoven, C, Chartier-Harlin, MC, Destée, A, Djarmati, A, Elbaz, A, Farrer, M, Ferrarese, C, Gibson, JM, Gispert, S, Hattori, N, Jasinska-Myga, B, Klein, C, Lesage, S, Lynch, T, Lichtner, P, Lambert, JC, Lang, AE, Mellick, GD, De Nigris, F, Opala, G, Quattrone, A, Riva, C, Rogaeva, E, Ross, OA, Satake, W, Silburn, PA, Theuns, J, Toda, T, Tomiyama, H, Uitti, RJ, Wirdefeldt, K, Wszolek, Z, Gasser, T & Krüger, R 2011, 'Role of sepiapterin reductase gene at the PARK3 locus in Parkinson's disease', Neurobiology of Aging, Jg. 32, Nr. 11. https://doi.org/10.1016/j.neurobiolaging.2011.05.024

TY - JOUR

T1 - Role of sepiapterin reductase gene at the PARK3 locus in Parkinson's disease

AU - Sharma, Manu

AU - Maraganore, Demetrius M.

AU - Ioannidis, John P.A.

AU - Riess, Olaf

AU - Aasly, Jan O.

AU - Annesi, Grazia

AU - Abahuni, Nadine

AU - Bentivoglio, Anna Rita

AU - Brice, Alexis

AU - Van Broeckhoven, Christine

AU - Chartier-Harlin, Marie Christine

AU - Destée, Alain

AU - Djarmati, Ana

AU - Elbaz, Alexis

AU - Farrer, Matthew

AU - Ferrarese, Carlo

AU - Gibson, J. Mark

AU - Gispert, Suzana

AU - Hattori, Nobutaka

AU - Jasinska-Myga, Barbara

AU - Klein, Christine

AU - Lesage, Suzanne

AU - Lynch, Timothy

AU - Lichtner, Peter

AU - Lambert, Jean Charles

AU - Lang, Anthony E.

AU - Mellick, George D.

AU - De Nigris, Francesa

AU - Opala, Grzegorz

AU - Quattrone, Aldo

AU - Riva, Chiara

AU - Rogaeva, Ekaterina

AU - Ross, Owen A.

AU - Satake, Wataru

AU - Silburn, Peter A.

AU - Theuns, Jessie

AU - Toda, Tatsushi

AU - Tomiyama, Hiroyuki

AU - Uitti, Ryan J.

AU - Wirdefeldt, Karin

AU - Wszolek, Zbigniew

AU - Gasser, Thomas

AU - Krüger, Rejko

PY - 2011/11/1

Y1 - 2011/11/1

N2 - 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. I 2 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.

AB - 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. I 2 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.

UR - https://www.scopus.com/pages/publications/80052624072

U2 - 10.1016/j.neurobiolaging.2011.05.024

DO - 10.1016/j.neurobiolaging.2011.05.024

M3 - Journal articles

C2 - 21782285

AN - SCOPUS:80052624072

SN - 0197-4580

VL - 32

JO - Neurobiology of Aging

JF - Neurobiology of Aging

IS - 11

ER -

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

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