Abstract:
: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.
journal_name
Neurobiol Agingjournal_title
Neurobiology of agingauthors
Fuchs J,Mueller JC,Lichtner P,Schulte C,Munz M,Berg D,Wüllner U,Illig T,Sharma M,Gasser Tdoi
10.1016/j.neurobiolaging.2007.08.014subject
Has Abstractpub_date
2009-05-01 00:00:00pages
731-8issue
5eissn
0197-4580issn
1558-1497pii
S0197-4580(07)00348-Xjournal_volume
30pub_type
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