Genetic association study on in and around the APOE in late-onset Alzheimer disease in Japanese.
The epsilon4 allele of APOE is a well-characterized genetic risk factor for late-onset Alzheimer disease (LOAD). Nevertheless, using high-density single nucleotide polymorphisms (SNPs), there have only been a few studies involving genetic association and linkage disequilibrium (LD) analyses of in and around the APOE. Here, we report fine mapping of a genomic region (about 200 kb) including the APOE in Japanese using 260 SNPs (mean intermaker distance, 0.77 kb). A case-control study demonstrated that 36 of these SNPs exhibited significance after adjustment for multiple testing. These SNPs are located in a genomic region including four genes, PVRL2, TOMM40, APOE and APOC1. Recombination rate estimation revealed that the associated region is firmly sandwiched between two recombination hotspots. Strong LD between these SNPs was observed (mean |D'|=0.914). These data suggest that the three genes other than APOE, i.e. PVRL2, TOMM40 and APOC1, could also yield a predisposition to LOAD.
Takei
Norihiro
N
Department of Molecular Genetics, Bioresource Science Branch, Center for Bioresources, Brain Research Institute, Niigata University, Niigata 951-8585, Japan.
Miyashita
Akinori
A
Tsukie
Tamao
T
Arai
Hiroyuki
H
Asada
Takashi
T
Imagawa
Masaki
M
Shoji
Mikio
M
Higuchi
Susumu
S
Urakami
Katsuya
K
Kimura
Hideo
H
Kakita
Akiyoshi
A
Takahashi
Hitoshi
H
Tsuji
Shoji
S
Kanazawa
Ichiro
I
Ihara
Yasuo
Y
Odani
Shoji
S
Kuwano
Ryozo
R
D017668:Age of Onset; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000235:genetics*; D053302:Apolipoprotein C-I / Q000235:genetics*; D001057:Apolipoproteins E / Q000235:genetics*; D044466:Asian People / Q000235:genetics; D015815:Cell Adhesion Molecules / Q000235:genetics*; D002874:Chromosome Mapping; D005260:Female; D008040:Genetic Linkage; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D026901:Membrane Transport Proteins / Q000235:genetics*; D008875:Middle Aged; D000090622:Mitochondrial Precursor Protein Import Complex Proteins; D000075983:Nectins
C505803:APOC1 protein, human; D053302:Apolipoprotein C-I; D001057:Apolipoproteins E; D015815:Cell Adhesion Molecules; D026901:Membrane Transport Proteins; D000090622:Mitochondrial Precursor Protein Import Complex Proteins; D000075983:Nectins; C400783:TOMM40 protein, human