Role of sepiapterin reductase gene at the PARK3 locus in Parkinson's disease
Loading...
Date
Authors
Sharma, M.
Maraganore, D. M.
Ioannidis, J. P.
Riess, O.
Aasly, J. O.
Annesi, G.
Abahuni, N.
Bentivoglio, A. R.
Brice, A.
Van Broeckhoven, C.
Journal Title
Journal ISSN
Volume Title
Publisher
Abstract
Type
Type of the conference item
Journal type
peer-reviewed
Educational material type
Conference Name
Journal name
Neurobiol Aging
Book name
Book series
Book edition
Alternative title / Subtitle
Description
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.
Description
Keywords
Alcohol Oxidoreductases/*genetics, Genetic Association Studies, Genetic Loci/*genetics, Genetic Predisposition to Disease, Genotype, Humans, Parkinson Disease/*genetics, Polymorphism, Single Nucleotide, Promoter Regions, Genetic
Subject classification
Citation
Link
http://www.ncbi.nlm.nih.gov/pubmed/21782285
http://ac.els-cdn.com/S0197458011002089/1-s2.0-S0197458011002089-main.pdf?_tid=3e842ac4b7511152dcf985037f828a05&acdnat=1333363327_3326c7d73c70349438798c2c46b97356
http://ac.els-cdn.com/S0197458011002089/1-s2.0-S0197458011002089-main.pdf?_tid=3e842ac4b7511152dcf985037f828a05&acdnat=1333363327_3326c7d73c70349438798c2c46b97356
Language
en
Publishing department/division
Advisor name
Examining committee
General Description / Additional Comments
Institution and School/Department of submitter
Πανεπιστήμιο Ιωαννίνων. Σχολή Επιστημών Υγείας. Τμήμα Ιατρικής