Genetic association analysis between TDP-43 polymorphisms and Alzheimer's disease in a Japanese population.
OBJECTIVE
A recent paper reported that the TAR-DNA binding protein (TDP-43) is the disease protein in amyotrophic lateral sclerosis and frontotemporal lobar dementia with ubiquitin-positive inclusions. In addition, it has been shown that TDP-43 may play a role in the pathogenesis of Alzheimer's disease (AD). This study aims to investigate whether single nucleotide polymorphisms (SNPs) of the TDP-43 gene are associated with AD.


METHODS
Eight SNPs, genotyped using TaqMan technology, were analyzed using a case-control study design including a haplotype analysis. Furthermore, an analysis of the cases divided according to apolipoprotein E (APO E) status was also carried out. Our case-control dataset consists of 181 AD patients and 130 age-matched controls.


RESULTS
Although none of the SNPs showed statistically significant association, we identified an association between a specific haplotype (G-A-A-G) of the TDP-43 gene and risk for AD. We could not confirm any synergetic association between the SNPs and APO E in our AD patients. Despite the relatively small sample size, our results indicate a possible genetic association between TDP- 43 and AD.


CONCLUSIONS
Further genetic studies are needed to clarify the relationship between the TDP-43 gene and AD.
Shibata
Nobuto
N
Department of Psychiatry, Juntendo University School of Medicine, Tokyo, Japan. nobuto.shibata@nifty.ne.jp
Ohnuma
Tohru
T
Baba
Hajime
H
Arai
Heii
H
D000368:Aged; D000544:Alzheimer Disease / Q000453:epidemiology* / Q000235:genetics*; D001057:Apolipoproteins E / Q000235:genetics; D016022:Case-Control Studies; D004247:DNA / Q000235:genetics / Q000302:isolation & purification; D004268:DNA-Binding Proteins / Q000235:genetics*; D030541:Databases, Genetic; D005260:Female; D005787:Gene Frequency; D006801:Humans; D007438:Introns / Q000235:genetics; D007564:Japan / Q000453:epidemiology; D015810:Linkage Disequilibrium / Q000235:genetics; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*
D001057:Apolipoproteins E; D004268:DNA-Binding Proteins; D004247:DNA