Association of transcription factor polymorphisms PITX3 and EN1 with Parkinson's disease.
The transcription factors PITX3 and Engrailed 1 (EN1), among others, have been shown to play a crucial role in the maturation and survival of midbrain dopaminergic neurons. The degeneration of those neurons is the pathological hallmark in Parkinson's disease (PD). In a hypothesis-driven candidate gene approach, it has been recently shown that polymorphisms in the genes coding for PITX3 and EN1 are associated with sporadic PD. In a study on 365 patients with PD and 418 controls, we genotyped nine single nucleotide polymorphisms spanning the entire genomic region of PITX3 and EN1. Furthermore, we analyzed whether the genotype of these SNPs associate with the age of onset in PD. We found a strong association between the PITX3 promoter rs3758549 polymorphism and PD (p=0.0001), as well as an association between EN1 rs1438852 and PD (p=0.046). In particular, our highly significant findings regarding the association of rs3758549 reproduce the results of the initial report on transcription factor gene variants, providing further evidence for PITX3 and EN1 polymorphisms as potential genetic risk factors for sporadic PD.
Haubenberger
Dietrich
D
Department of Neurology, Medical University of Vienna, Währinger Gürtel 18-20, A-1090 Vienna, Austria. dietrich.haubenberger@meduniwien.ac.at
Reinthaler
Eva
E
Mueller
Jakob C
JC
Pirker
Walter
W
Katzenschlager
Regina
R
Froehlich
Roman
R
Bruecke
Thomas
T
Daniel
Gerhard
G
Auff
Eduard
E
Zimprich
Alexander
A
D000368:Aged; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study / Q000379:methods; D005838:Genotype; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010300:Parkinson Disease / Q000235:genetics*; D011110:Polymorphism, Genetic / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics*
C513076:EN1 protein, human; D018398:Homeodomain Proteins; D014157:Transcription Factors; C433629:homeobox protein PITX3