BRG1 variant rs1122608 on chromosome 19p13.2 confers protection against stroke and regulates expression of pre-mRNA-splicing factor SFRS3.
BRG1 variant rs1122608 on chromosome 19p13.2 confers protection against stroke and regulates expression of pre-mRNA-splicing factor SFRS3.
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DOI：
10.1007/s00439-013-1389-x
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发表时间：
2014-05
期刊：
影响因子：
5.3
通讯作者：
Wang, Qing K.
中科院分区：
文献类型：
--
作者：
Xiong, Xin;Xu, Chengqi;Zhang, Yuting;Li, Xiuchun;Wang, Binbin;Wang, Fan;Yang, Qin;Wang, Dan;Wang, Xiaojing;Li, Sisi;Chen, Shanshan;Zhao, Yuanyuan;Yin, Dan;Huang, Yufeng;Zhu, Xuan;Wang, Li;Wang, Longfei;Chang, Le;Xu, Chaoping;Li, Hui;Ke, Tie;Ren, Xiang;Wu, Yanxia;Zhang, Rongfeng;Wu, Tangchun;Xia, Yunlong;Yang, Yanzong;Ma, Xu;Tu, Xin;Wang, Qing K.
染色体19p13.2上的单核苷酸多态(SNP)rs1122608和BRG1/SMARCA4基因以前被认为与冠心病(CAD)相关。冠心病和缺血性中风都与动脉粥样硬化有关。因此，我们检验了rs1122608与缺血性中风相关的假设。进一步的研究被用来确定rs1122608调节动脉粥样硬化的最可能的机制。在病例对照研究中，使用了两个独立的中国汉族ID基因队列，包括1,075例病例和2,685名对照的中央队列和1,208例病例和824名对照的北方队列。利用eQTL和实时荧光定量RT-PCR法对受rs1122608影响的候选基因(S)进行定位。在中心基因队列中，SNPrs1122608的小等位基因T与降低缺血性卒中的风险显著相关(调整后的PADJ=2.1×10−4，OR 0.6 1)。这种关联在一个独立的北方基因ID队列中重复(PADJ=6.00×10−3，或0.69)。这种关联在联合群体中变得更为显著(PADJ=7.86×10−5，或0.73)。SNP rs1122608等位基因T也与总胆固醇水平降低显著相关(PADJ=0.013)。Rs1122608的T等位基因与编码剪接调控基因的SFRS3的表达增加有关，而与BRG1/SMARCA4或LDLR(位于rs1122608的36kb)的表达无关。SFSR3表达增加可能会降低IL-1β的表达和分泌，从而降低动脉粥样硬化和中风的风险。这是第一项证明rs1122608对缺血性中风具有保护作用并在疾病过程中涉及剪接因子SFSR3的研究。
A single nucleotide polymorphism (SNP) rs1122608 on chromosome 19p13.2 and in the BRG1/SMARCA4 gene was previously associated with coronary artery disease (CAD). CAD and ischemic stroke are both associated with atherosclerosis. Thus, we tested the hypothesis that rs1122608 is associated with ischemic stroke. Further studies were used to identify the most likely mechanism by which rs1122608 regulates atherosclerosis. For case–control association studies, two independent Chinese Han GeneID cohorts were used, including a Central cohort with 1,075 cases and 2,685 controls and the Northern cohort with 1,208 cases and 824 controls. eQTL and real-time RT-PCR analyses were used to identify the potential candidate gene(s) affected by rs1122608. The minor allele T of SNP rs1122608 showed significant association with a decreased risk of ischemic stroke in the Central GeneID cohort (adjusted Padj = 2.1 × 10−4, OR 0.61). The association was replicated in an independent Northern GeneID cohort (Padj = 6.00 × 10−3, OR 0.69). The association became more significant in the combined population (Padj = 7.86 × 10−5, OR 0.73). Allele T of SNP rs1122608 also showed significant association with a decreased total cholesterol level (Padj = 0.013). Allele T of rs1122608 was associated with an increased expression level of SFRS3 encoding an mRNA splicing regulator, but not with the expression of BRG1/SMARCA4 or LDLR (located 36 kb from rs1122608). Increased expression of SFSR3 may decrease IL-1β expression and secretion, resulting in reduced risk of atherosclerosis and stroke. This is the first study that demonstrates that rs1122608 confers protection against ischemic stroke and implicates splicing factor SFSR3 in the disease process.
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影响因子：
4.6
作者：
Chiba T;Itoh T;Tabuchi M;Nakazawa T;Satou T
通讯作者：
Satou T
影响因子：
8.3
作者：
Bevan, Steve;Traylor, Matthew;Markus, Hugh S.
通讯作者：
Markus, Hugh S.
影响因子：
5.3
作者：
Lu, Yingchang;Feskens, Edith J. M.;Dolle, Martijn E. T.
通讯作者：
Dolle, Martijn E. T.
DOI：
10.1016/s1474-4422(12)70234-x
发表时间：
2012-11
期刊：
The Lancet. Neurology
影响因子：
--
作者：
Traylor M;Farrall M;Holliday EG;Sudlow C;Hopewell JC;Cheng YC;Fornage M;Ikram MA;Malik R;Bevan S;Thorsteinsdottir U;Nalls MA;Longstreth W;Wiggins KL;Yadav S;Parati EA;Destefano AL;Worrall BB;Kittner SJ;Khan MS;Reiner AP;Helgadottir A;Achterberg S;Fernandez-Cadenas I;Abboud S;Schmidt R;Walters M;Chen WM;Ringelstein EB;O'Donnell M;Ho WK;Pera J;Lemmens R;Norrving B;Higgins P;Benn M;Sale M;Kuhlenbäumer G;Doney AS;Vicente AM;Delavaran H;Algra A;Davies G;Oliveira SA;Palmer CN;Deary I;Schmidt H;Pandolfo M;Montaner J;Carty C;de Bakker PI;Kostulas K;Ferro JM;van Zuydam NR;Valdimarsson E;Nordestgaard BG;Lindgren A;Thijs V;Slowik A;Saleheen D;Paré G;Berger K;Thorleifsson G;Australian Stroke Genetics Collaborative, Wellcome Trust Case Control Consortium 2 (WTCCC2);Hofman A;Mosley TH;Mitchell BD;Furie K;Clarke R;Levi C;Seshadri S;Gschwendtner A;Boncoraglio GB;Sharma P;Bis JC;Gretarsdottir S;Psaty BM;Rothwell PM;Rosand J;Meschia JF;Stefansson K;Dichgans M;Markus HS;International Stroke Genetics Consortium
通讯作者：
International Stroke Genetics Consortium
染色体4q25上的rs2200733与中国汉族人群心房颤动和缺血性脑卒中的关联评估
影响因子：
5.3
作者：
Shi, Lisong;Li, Cong;Wang, Qing Kenneth
通讯作者：
Wang, Qing Kenneth