Identifying differential regulatory control of APOE ɛ4 on African versus European haplotypes as potential therapeutic targets.
Identifying differential regulatory control of APOE ɛ4 on African versus European haplotypes as potential therapeutic targets.
复制标题
DOI：
10.1002/alz.12534
复制
发表时间：
2022-10
期刊：
影响因子：
--
通讯作者：
中科院分区：
文献类型：
--
作者：
We previously demonstrated that in Alzheimer’s disease (AD) patients, European apolipoprotein E (APOE) ε4 carriers express significantly more APOEε4 in their brains than African AD carriers. We examined single nucleotide polymorphisms near APOE with significant frequency differences between African and European/Japanese APOE ε4 haplotypes that could contribute to this difference in expression through regulation. Two enhancer massively parallel reporter assay (MPRA) approaches were performed, supplemented with single fragment reporter assays. We used Capture C analyses to support interactions with the APOE promoter. Introns within TOMM40 showed increased enhancer activity in the European/Japanese versus African haplotypes in astrocytes and microglia. This region overlaps with APOE promoter interactions as assessed by Capture C analysis. Single variant analyses pinpoints rs2075650/rs157581, and rs59007384 as functionally different on these haplotypes. Identification of the mechanisms for differential regulatory function for APOE expression between African and European/Japanese haplotypes could lead to therapeutic targets for APOE ε4 carriers.
登录
查看更多内容
APOE 位点遗传变异的功能分析表明区域增强子参与 TOMM40 和 APOE 的调节。
影响因子：
3.5
作者：
通讯作者：
--
影响因子：
3.9
作者：
Choi, Kookhwan;Chun, Jaeyoung;Kim, Joo Sung
通讯作者：
Kim, Joo Sung
影响因子：
3.5
作者：
Bray, NJ;Jehu, L;O'Donovan, MC
通讯作者：
O'Donovan, MC
影响因子：
16.6
作者：
Chesi, Alessandra;Wagley, Yadav;Grant, Struan F. A.
通讯作者：
Grant, Struan F. A.
影响因子：
64.8
作者：
Roadmap Epigenomics Consortium;Kundaje A;Meuleman W;Ernst J;Bilenky M;Yen A;Heravi-Moussavi A;Kheradpour P;Zhang Z;Wang J;Ziller MJ;Amin V;Whitaker JW;Schultz MD;Ward LD;Sarkar A;Quon G;Sandstrom RS;Eaton ML;Wu YC;Pfenning AR;Wang X;Claussnitzer M;Liu Y;Coarfa C;Harris RA;Shoresh N;Epstein CB;Gjoneska E;Leung D;Xie W;Hawkins RD;Lister R;Hong C;Gascard P;Mungall AJ;Moore R;Chuah E;Tam A;Canfield TK;Hansen RS;Kaul R;Sabo PJ;Bansal MS;Carles A;Dixon JR;Farh KH;Feizi S;Karlic R;Kim AR;Kulkarni A;Li D;Lowdon R;Elliott G;Mercer TR;Neph SJ;Onuchic V;Polak P;Rajagopal N;Ray P;Sallari RC;Siebenthall KT;Sinnott-Armstrong NA;Stevens M;Thurman RE;Wu J;Zhang B;Zhou X;Beaudet AE;Boyer LA;De Jager PL;Farnham PJ;Fisher SJ;Haussler D;Jones SJ;Li W;Marra MA;McManus MT;Sunyaev S;Thomson JA;Tlsty TD;Tsai LH;Wang W;Waterland RA;Zhang MQ;Chadwick LH;Bernstein BE;Costello JF;Ecker JR;Hirst M;Meissner A;Milosavljevic A;Ren B;Stamatoyannopoulos JA;Wang T;Kellis M
通讯作者：
Kellis M