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Fuchs, J.* ; Mueller, J.C.* ; Lichtner, P. ; Schulte, C.* ; Münz, M.* ; Berg, D.* ; Wüllner, U.* ; Illig, T. ; Sharma, M.* ; Gasser, T.*

The transcription factor PITX3 is associated with sporadic Parkinson's disease.

Neurobiol. Aging 30, 731-738 (2009)
DOI PMC
Open Access Green as soon as Postprint is submitted to ZB.
Parkinson's disease (PD) is a progressive neurodegenerative disease with typical motor symptoms due to the preferential loss of midbrain dopaminergic (mDA) neurons in the Substantia nigra pars compacta. Several proteins of the homeodomain family are crucial for the development of mDA neurons. These proteins remain expressed into adulthood with largely unknown functions, but potentially influence mDA neuronal survival. To determine whether genetic variation in these genes plays a role in sporadic PD, we performed a genetic association study in a screening sample of 340 PD patients and 680 controls and a large replication sample of 669 PD patients and 669 controls using 54 single nucleotide polymorphisms in and around the Engrailed 1/2, PITX3, LMX1B and OTX2 genes. We provide evidence for a novel, strong and reproducible association of the PITX3 promoter SNP rs3758549: C > T (p = 0.004) with PD. The C-allele appears to be a recessive risk allele with an estimated population frequency of 83%. An allele-dependent dysregulation of PITX3 expression might contribute to the susceptibility to PD.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords Parkinson's disease; PITX3; Homeoproteins; SNPs; Midbrain dopaminergic neurons; Association study; Neuronal development; mesencephalic dopaminergic-neurons; alpha-synuclein; aphakia mice; brain expression; ventral midbrain; engrailed genes; homeobox gene; nurr1; mutation; differentiation
ISSN (print) / ISBN 0197-4580
e-ISSN 1558-1497
Journal Neurobiology of Aging
Quellenangaben Volume: 30, Issue: 5, Pages: 731-738 Article Number: , Supplement: ,
Publisher Elsevier
Publishing Place New York, NY [u.a.]
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Institute of Human Genetics (IHG)
Institute of Epidemiology (EPI)