Significant Association Between CAV1 Variant rs3807989 on 7p31 and Atrial Fibrillation in a Chinese Han Population
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‐nucleo...
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| Format: | Article |
| Language: | English |
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Wiley
2015-05-01
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| Series: | Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease |
| Subjects: | |
| Online Access: | https://doi.org/10.1161/JAHA.115.001980 |
| _version_ | 1798000449944551424 |
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| author | Shanshan Chen Chuchu Wang Xiaojing Wang Chengqi Xu Manman Wu Pengxia Wang Xin Tu Qing K. Wang |
| author_facet | Shanshan Chen Chuchu Wang Xiaojing Wang Chengqi Xu Manman Wu Pengxia Wang Xin Tu Qing K. Wang |
| author_sort | Shanshan Chen |
| collection | DOAJ |
| description | 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. |
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| spelling | doaj.art-43f9e1b7f63945c29b6690cd3b9c92f02022-12-22T04:27:06ZengWileyJournal of the American Heart Association: Cardiovascular and Cerebrovascular Disease2047-99802015-05-0145n/an/a10.1161/JAHA.115.001980Significant Association Between CAV1 Variant rs3807989 on 7p31 and Atrial Fibrillation in a Chinese Han PopulationShanshan Chen0Chuchu Wang1Xiaojing Wang2Chengqi Xu3Manman Wu4Pengxia Wang5Xin Tu6Qing K. Wang7Key Laboratory of Molecular Biophysics of the Ministry of Education Cardio‐X Institute College of Life Science and Technology and Center for Human Genome Research Huazhong University of Science and Technology Wuhan ChinaKey Laboratory of Molecular Biophysics of the Ministry of Education Cardio‐X Institute College of Life Science and Technology and Center for Human Genome Research Huazhong University of Science and Technology Wuhan ChinaKey Laboratory of Molecular Biophysics of the Ministry of Education Cardio‐X Institute College of Life Science and Technology and Center for Human Genome Research Huazhong University of Science and Technology Wuhan ChinaKey Laboratory of Molecular Biophysics of the Ministry of Education Cardio‐X Institute College of Life Science and Technology and Center for Human Genome Research Huazhong University of Science and Technology Wuhan ChinaKey Laboratory of Molecular Biophysics of the Ministry of Education Cardio‐X Institute College of Life Science and Technology and Center for Human Genome Research Huazhong University of Science and Technology Wuhan ChinaKey Laboratory of Molecular Biophysics of the Ministry of Education Cardio‐X Institute College of Life Science and Technology and Center for Human Genome Research Huazhong University of Science and Technology Wuhan ChinaKey Laboratory of Molecular Biophysics of the Ministry of Education Cardio‐X Institute College of Life Science and Technology and Center for Human Genome Research Huazhong University of Science and Technology Wuhan ChinaKey Laboratory of Molecular Biophysics of the Ministry of Education Cardio‐X Institute College of Life Science and Technology and Center for Human Genome Research Huazhong University of Science and Technology Wuhan ChinaBackground 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.https://doi.org/10.1161/JAHA.115.001980atrial fibrillationCAV1genome‐wide association studies (GWAS)rs3807989single‐nucleotide polymorphism |
| spellingShingle | Shanshan Chen Chuchu Wang Xiaojing Wang Chengqi Xu Manman Wu Pengxia Wang Xin Tu Qing K. Wang Significant Association Between CAV1 Variant rs3807989 on 7p31 and Atrial Fibrillation in a Chinese Han Population Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease atrial fibrillation CAV1 genome‐wide association studies (GWAS) rs3807989 single‐nucleotide polymorphism |
| title | Significant Association Between CAV1 Variant rs3807989 on 7p31 and Atrial Fibrillation in a Chinese Han Population |
| title_full | Significant Association Between CAV1 Variant rs3807989 on 7p31 and Atrial Fibrillation in a Chinese Han Population |
| title_fullStr | Significant Association Between CAV1 Variant rs3807989 on 7p31 and Atrial Fibrillation in a Chinese Han Population |
| title_full_unstemmed | Significant Association Between CAV1 Variant rs3807989 on 7p31 and Atrial Fibrillation in a Chinese Han Population |
| title_short | Significant Association Between CAV1 Variant rs3807989 on 7p31 and Atrial Fibrillation in a Chinese Han Population |
| title_sort | significant association between cav1 variant rs3807989 on 7p31 and atrial fibrillation in a chinese han population |
| topic | atrial fibrillation CAV1 genome‐wide association studies (GWAS) rs3807989 single‐nucleotide polymorphism |
| url | https://doi.org/10.1161/JAHA.115.001980 |
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