Lack of genetic association of the UCHL1 gene with Alzheimer's disease and Parkinson's disease with dementia.
OBJECTIVE
Several candidate genes were suggested to modify the susceptibility to both Alzheimer's disease (AD) and Parkinson's disease (PD). Symptoms of dementia are found in approximately 30% of PD patients. Both apolipoprotein E (APO E) and ubiquitin carboxyl-terminal esterase L1 (UCHL1) are neuropathogenic proteins for both diseases. The aim of this study was to investigate whether polymorphisms of both genes are associated with AD and PD with dementia (PDD).


METHODS
The APO E polymorphism and 5 common single-nucleotide polymorphisms (SNPs) of the UCHL1 gene were analyzed using a case-control study design.


RESULTS
Although APO E4 affected the onset of AD, the 5 SNPs of the UCHL1 gene were not associated with risk for AD. Linkage disequilibrium (LD) analysis of our Japanese data set showed that the SNPs of the UCHL1 gene are part of one LD block. Although one SNP, rs4861387, of the UCHL1 gene showed marginal association with PDD, we did not detect any association between the other SNPs and PDD.


CONCLUSIONS
The common SNPs of UCHL1 are not major risk factors for AD. Since our analyses on PDD are preliminary, further genetic studies on APO E, UCHL1 and PD with and without dementia are needed.
Department of Psychiatry, Juntendo University School of Medicine, Tokyo, Japan. nshibata@juntendo.ac.jp
Nobuto
N
Shibata
Yumiko
Y
Motoi
Hiroyuki
H
Tomiyama
Tohru
T
Ohnuma
Bolati
B
Kuerban
Katrin
K
Tomson
Miwa
M
Komatsu
Nobutaka
N
Hattori
Heii
H
Arai
D000368:Aged; D000544:Alzheimer Disease / Q000453:epidemiology / Q000235:genetics*; D001057:Apolipoproteins E / Q000235:genetics; D016022:Case-Control Studies; D004247:DNA / Q000235:genetics; D016208:Databases, Factual; D003704:Dementia / Q000453:epidemiology / Q000235:genetics*; D005260:Female; D006801:Humans; D007564:Japan / Q000453:epidemiology; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D010300:Parkinson Disease / Q000453:epidemiology / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D043222:Ubiquitin Thiolesterase / Q000235:genetics*
D001057:Apolipoproteins E; C482860:UCHL1 protein, human; D004247:DNA; D043222:Ubiquitin Thiolesterase