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
14 Zitate (Scopus)


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.

ZeitschriftNeurobiology of Aging
PublikationsstatusVeröffentlicht - 01.11.2011


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