Significant Association Between CAV1 Variant rs3807989 on 7p31 and Atrial Fibrillation in a Chinese Han Population.
Significant Association Between CAV1 Variant rs3807989 on 7p31 and Atrial Fibrillation in a Chinese Han Population.
复制标题
中国汉族人群中 7p31 上的 CAV1 变异 rs3807989 与心房颤动之间的显着关联
DOI：
10.1161/jaha.115.001980
复制
发表时间：
2015-05-07
影响因子：
5.4
通讯作者：
Wang QK
中科院分区：
文献类型：
--
作者：
Chen S;Wang C;Wang X;Xu C;Wu M;Wang P;Tu X;Wang QK
背景：最近在欧洲血统人群中进行的全基因组关联研究揭示了几个与房颤相关的基因组位点。我们以前在中国人群中复制了4q25基因座(PITX2)和16q22基因座(ZFHX3)，但没有在1q21上复制KCNN3基因座。然而，CAV1编码小窝蛋白-1的单核苷酸多态性rs3807989在两个中国复制研究中报道了有争议的结果。方法与结果在941例中国汉族人群和562名正常对照人群中，对其余6个房颤基因座rs3807989/CAV1、rs593479/Prrx1、rs6479562/C9orf3、rs10824026/SYNPO2L、rs1152591/SYNE2和rs7164883/HCN4进行了分析。仅rs3807989与房颤有显著关联(PADJ=4.77×10−5)，该结果在另外两个独立人群中重复，分别为709例病例和2 175例对照、463例病例和644例对照以及2113例病例和3381例对照的联合人群(PADJ=2.2 0×10−9；主要等位基因G的优势比[OR]=1.3 4)。Meta分析结合中国和日本人群以往报道的数据，也显示rs3807989与房颤有显著关联(P=3.4 0×10−4；等位基因G的OR=1.2 4)。我们还发现rs3807989在3个独立群体和联合群体中与孤立性房颤显著相关(PADJ=3.85×10−8；主等位基因G的OR=1.43)。结论在中国汉族人群中，rs3807989基因与房颤之间存在显著的相关性。CAV1与钾通道Kir2.1、KCNH2和HCN4以及钠通道NaV1.5和Nav1.8相互作用，使CAV1成为不同民族人群房颤的候选易感基因。这项研究首次表明rs3807989与孤立性房颤之间存在显著的相关性。
Background Recent genome-wide association studies (GWAS) in European ancestry populations revealed several genomic loci for atrial fibrillation (AF). We previously replicated the 4q25 locus (PITX2) and 16q22 locus (ZFHX3) in the Chinese population, but not the KCNN3 locus on 1q21. With single-nucleotide polymorphism rs3807989 in CAV1 encoding caveolin-1, however, controversial results were reported in 2 Chinese replication studies. Methods and Results Six remaining AF genetic loci from GWAS, including rs3807989/CAV1, rs593479/PRRX1, rs6479562/C9orf3, rs10824026/SYNPO2L, rs1152591/SYNE2, and rs7164883/HCN4, were analyzed in a Chinese Han population with 941 cases and 562 controls. Only rs3807989 showed significant association with AF (Padj=4.77×10−5), and the finding was replicated in 2 other independent populations with 709 cases and 2175 controls, 463 cases and 644 controls, and the combined population with a total of 2113 cases and 3381 controls (Padj=2.20×10−9; odds ratio [OR]=1.34 for major allele G). Meta-analysis, together with data from previous reports in Chinese and Japanese populations, also showed a significant association between rs3807989 and AF (P=3.40×10−4; OR=1.24 for allele G). We also found that rs3807989 showed a significant association with lone AF in 3 independent populations and in the combined population (Padj=3.85×10−8; OR=1.43 for major allele G). Conclusions The data in this study revealed a significant association between rs3807989 and AF in the Chinese Han population. Together with the findings that caveolin-1 interacts with potassium channels Kir2.1, KCNH2, and HCN4 and sodium channels Nav1.5 and Nav1.8, CAV1 becomes a strong candidate susceptibility gene for AF across different ethnic populations. This study is the first to show a significant association between rs3807989 and lone AF.