Genetic association study on in and around the APOE in late-onset Alzheimer disease in Japanese.

Abstract The ɛ 4 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.