Promoter Polymorphism-219T/G is an Effect Modifier of the Influence of ε4 on Alzheimer's Disease Risk in a Multiracial Sample.

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ID: 22175
2019
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Abstract
Variants in the gene region may explain ethnic differences in the association of Alzheimer's disease (AD) with ε4. Ethnic differences in allele frequencies for three 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 promoter SNP rs405509 alleles in EastAs : OR (odds ratio) = 27.02, = 8.80 × 10; : OR = 15.87, = 2.62 × 10) and EuroAs (: OR = 18.13, = 2.69 × 10; : OR = 12.63, = 3.44 × 10), and rs405509- homozygotes had a younger onset and more severe cortical atrophy than those with -allele. Functional experiments using promoter fragments demonstrated that lowered 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 expression might lower AD risk among ε4 homozygotes.
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Authors Choi, Kyu Yeong;Lee, Jang Jae;Gunasekaran, Tamil Iniyan;Kang, Sarang;Lee, Wooje;Jeong, Jangho;Lim, Ho Jae;Zhang, Xiaoling;Zhu, Congcong;Won, So-Yoon;Choi, Yu Yong;Seo, Eun Hyun;Lee, Seok Cheol;Gim, Jungsoo;Chung, Ji Yeon;Chong, Ari;Byun, Min Soo;Seo, Sujin;Ko, Pan-Woo;Han, Ji-Won;McLean, Catriona;Farrell, John;Lunetta, Kathryn L;Miyashita, Akinori;Hara, Norikazu;Won, Sungho;Choi, Seong-Min;Ha, Jung-Min;Jeong, Jee Hyang;Kuwano, Ryozo;Song, Min Kyung;An, Seong Soo A;Lee, Young Min;Park, Kyung Won;Lee, Ho-Won;Choi, Seong Hye;Rhee, Sangmyung;Song, Woo Keun;Lee, Jung Sup;Mayeux, Richard;Haines, Jonathan L;Pericak-Vance, Margaret A;Choo, I L Han;Nho, Kwangsik;Kim, Ki-Woong;Lee, Dong Young;Kim, SangYun;Kim, Byeong C;Kim, Hoowon;Jun, Gyungah R;Schellenberg, Gerard D;Ikeuchi, Takeshi;Farrer, Lindsay A;Lee, Kun Ho;Neuroimaging Initative, Alzheimer's Disease;
Journal journal of clinical medicine
Year 2019
DOI
E1236
URL
Keywords Keywords not found

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