Year-end Sale % OFF 
Abstract
Variants in the APOE gene region may explain ethnic differences in the association of Alzheimer’s disease (AD) with ε4. Ethnic differences in allele frequencies for three APOE region SNPs (single nucleotide polymorphisms) were identified and tested for association in 19,398 East Asians (EastA), including Koreans and Japanese, 15,836 European ancestry (EuroA) individuals, and 4985 African Americans, and with brain imaging measures of cortical atrophy in sub-samples of Koreans and EuroAs. Among ε4/ε4 individuals, AD risk increased substantially in a dose-dependent manner with the number of APOE promoter SNP rs405509 T alleles in EastAs (TT: OR (odds ratio) = 27.02, p = 8.80 × 10−94; GT: OR = 15.87, p = 2.62 × 10−9) and EuroAs (TT: OR = 18.13, p = 2.69 × 10−108; GT: OR = 12.63, p = 3.44 × 10−64), and rs405509-T homozygotes had a younger onset and more severe cortical atrophy than those with G-allele. Functional experiments using APOE promoter fragments demonstrated that TT lowered APOE expression in human brain and serum. The modifying effect of rs405509 genotype explained much of the ethnic variability in the AD/ε4 association, and increasing APOE expression might lower AD risk among ε4 homozygotes.
Highlights
Alzheimer’s disease (AD) is a progressive neurodegenerative disorder, characterized clinically by dementia and memory loss
principal components (PCs) identified by these analyses that are significantly associated with AD were included in association test models for Koreans (n = 4), Japanese (n = 5), and combined East Asians (EastA) (n = 3)
The distributions of apolipoprotein E (APOE) genotypes and allele frequencies were significantly different between AD cases and controls in all ethnic groups (Tables S3 and S4) with increasing odds of AD among carriers of the ε4 allele in a dose-dependent manner and lower odds of AD among ε2 carriers (Table 1 and Tables S5)
Summary
Alzheimer’s disease (AD) is a progressive neurodegenerative disorder, characterized clinically by dementia and memory loss. Variability across populations in the risk of AD associated with genotypes containing ε4 can be explained, in part, by differences in the ε4 allele frequency, i.e., groups with a higher frequency of ε4 trend toward a lower risk of AD attributable to ε4 [28,29] This pattern most notably occurs in populations of African ancestry who have one of the world’s highest frequencies of ε4 but the lowest prevalence of AD [10,28,30]. The basis for population differences in the AD/ε4 association is unknown, but several hypotheses have been proposed, including genetic modifiers within or extant from the APOE locus and moderating influences of dietary and environmental factors [31] To address this question, we investigated the ethnic-dependent risk of AD mediated by other APOE single nucleotide polymorphisms (SNPs) in the coding and regulatory regions in a multi-ethnic sample. We examined the influence of APOE SNPs on brain structure, including cortical thickness and hippocampal volume
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
