TY - JOUR
T1 - LINGO1 is not associated with Parkinson's disease in German patients
AU - Klebe, Stephan
AU - Thier, Sandra
AU - Lorenz, Delia
AU - Nothnagel, Michael
AU - Schreiber, Stefan
AU - Klein, Christine
AU - Hagenah, Johann
AU - Kasten, Meike
AU - Berg, Daniela
AU - Srulijes, Karin
AU - Gasser, Thomas
AU - Deuschl, Günther
AU - Kuhlenbäumer, Gregor
PY - 2010/9/1
Y1 - 2010/9/1
N2 - Essential tremor (ET) and Parkinson's disease (PD) are the most common movement disorders and show clinical, genetic, and pathophysiological overlap. Single-nucleotide polymorphisms (SNPs) in the leucine-rich repeat (LRR) and immunoglobulin (Ig) domain-containing, Nogo receptor-interacting protein gene (LINGO1) are associated with ET. LINGO1 is overexpressed in the substantia nigra (SN) of PD patients and inhibition of LINGO1 confers neuroprotection in a rodent model of PD. In this study we test the hypothesis whether SNPs in the LINGO1 gene that are associated with ET are also associated with PD. Three large German case-control samples from Kiel, Lübeck, and Tübingen (total: 1,798 cases and 1,482 controls) were genotyped for the three LINGO1 SNPs associated with ET. Association was assessed using allele- and genotype-based tests in each of the three samples separately, in the combined sample, and in subsets of patients with early-onset PD (<50 years) and of patients with a positive family history of PD. Neither of the three samples alone nor the combined sample showed evidence for association between LINGO1 SNPs and PD. The allele-based test showed a trend toward nominal association for all three SNPs in the Kiel sample. The subsets with early-onset PD or a positive family history did also not reveal evidence for association. SNPs in the LINGO1 gene associated with ET could not be shown to be associated with PD in our study population, despite a postulated overlap between both diseases.
AB - Essential tremor (ET) and Parkinson's disease (PD) are the most common movement disorders and show clinical, genetic, and pathophysiological overlap. Single-nucleotide polymorphisms (SNPs) in the leucine-rich repeat (LRR) and immunoglobulin (Ig) domain-containing, Nogo receptor-interacting protein gene (LINGO1) are associated with ET. LINGO1 is overexpressed in the substantia nigra (SN) of PD patients and inhibition of LINGO1 confers neuroprotection in a rodent model of PD. In this study we test the hypothesis whether SNPs in the LINGO1 gene that are associated with ET are also associated with PD. Three large German case-control samples from Kiel, Lübeck, and Tübingen (total: 1,798 cases and 1,482 controls) were genotyped for the three LINGO1 SNPs associated with ET. Association was assessed using allele- and genotype-based tests in each of the three samples separately, in the combined sample, and in subsets of patients with early-onset PD (<50 years) and of patients with a positive family history of PD. Neither of the three samples alone nor the combined sample showed evidence for association between LINGO1 SNPs and PD. The allele-based test showed a trend toward nominal association for all three SNPs in the Kiel sample. The subsets with early-onset PD or a positive family history did also not reveal evidence for association. SNPs in the LINGO1 gene associated with ET could not be shown to be associated with PD in our study population, despite a postulated overlap between both diseases.
UR - http://www.scopus.com/inward/record.url?scp=77956105396&partnerID=8YFLogxK
U2 - 10.1002/ajmg.b.31085
DO - 10.1002/ajmg.b.31085
M3 - Journal articles
C2 - 20468067
AN - SCOPUS:77956105396
SN - 1552-4841
VL - 153
SP - 1173
EP - 1178
JO - American Journal of Medical Genetics, Part B: Neuropsychiatric Genetics
JF - American Journal of Medical Genetics, Part B: Neuropsychiatric Genetics
IS - 6
ER -