View : 54 Download: 0

APOE Promoter Polymorphism-219T/G is an Effect Modifier of the Influence of APOE epsilon 4 on Alzheimer's Disease Risk in a Multiracial Sample

Title
APOE Promoter Polymorphism-219T/G is an Effect Modifier of the Influence of APOE epsilon 4 on Alzheimer's Disease Risk in a Multiracial Sample
Authors
Choi, Kyu YeongLee, Jang JaeGunasekaran, Tamil IniyanKang, SarangLee, WoojeJeong, JanghoLim, Ho JaeZhang, XiaolingZhu, CongcongWon, So-YoonChoi, Yu YongSeo, Eun HyunLee, Seok CheolGim, JungsooChung, Ji YeonChong, AriByun, Min SooSeo, SujinKo, Pan-WooHan, Ji-WonMcLean, CatrionaFarrell, JohnLunetta, Kathryn L.Miyashita, AkinoriHara, NorikazuWon, SunghoChoi, Seong-MinHa, Jung-MinJeong, Jee HyangKuwano, RyozoSong, Min KyungAn, Seong Soo A.Lee, Young MinPark, Kyung WonLee, Ho-WonChoi, Seong HyeRhee, SangmyungSong, Woo KeunLee, Jung SupMayeux, RichardHaines, Jonathan L.Pericak-Vance, Margaret A.Choo, Il HanNho, KwangsikKim, Ki-WoongLee, Dong YoungKim, SangYunKim, Byeong C.Kim, HoowonJun, Gyungah R.Schellenberg, Gerard D.Ikeuchi, TakeshiFarrer, Lindsay A.Lee, Kun HoAlzheimer's Dis Neuroimaging Inita
Ewha Authors
정지향
SCOPUS Author ID
정지향scopus
Issue Date
2019
Journal Title
JOURNAL OF CLINICAL MEDICINE
ISSN
2077-0383JCR Link
Citation
JOURNAL OF CLINICAL MEDICINE vol. 8, no. 8
Keywords
APOEpromoter polymorphismAlzheimer's diseaseethnic variabilitybrain atrophygenetic association
Publisher
MDPI
Indexed
SCIE; SCOPUS WOS
Document Type
Article
Abstract
Variants in the APOE gene region may explain ethnic differences in the association of Alzheimer's disease (AD) with epsilon 4. 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 epsilon 4/epsilon 4 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 x 10(-94); GT: OR = 15.87, p = 2.62 x 10(-9)) and EuroAs (TT: OR = 18.13, p = 2.69 x 10(-108); GT: OR = 12.63, p = 3.44 x 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/epsilon 4 association, and increasing APOE expression might lower AD risk among epsilon 4 homozygotes.
DOI
10.3390/jcm8081236
Appears in Collections:
의과대학 > 의학과 > Journal papers
Files in This Item:
There are no files associated with this item.
Export
RIS (EndNote)
XLS (Excel)
XML


qrcode

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.

BROWSE