Open AccessSignificant Association Between CAV 1 Variant rs3807989 on 7p31 and Atrial Fibrillation in a Chinese Han Population
Author(s) -
Chen Shanshan,
Wang Chuchu,
Wang Xiaojing,
Xu Chengqi,
Wu Manman,
Wang Pengxia,
Tu Xin,
Wang Qing K.
Publication year - 2015
Publication title -
journal of the american heart association
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.494
H-Index - 85
ISSN - 2047-9980
DOI - 10.1161/jaha.115.001980
Subject(s) - genome wide association study , locus (genetics) , genetics , odds ratio , allele , medicine , single nucleotide polymorphism , genetic association , population , biology , genotype , gene , environmental health
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 ( PITX 2 ) and 16q22 locus ( ZFHX 3 ) in the Chinese population, but not the KCNN 3 locus on 1q21. With single‐nucleotide polymorphism rs3807989 in CAV 1 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/ CAV 1 , rs593479/ PRRX 1 , rs6479562/ C9orf3 , rs10824026/ SYNPO 2L , rs1152591/ SYNE 2 , and rs7164883/ HCN 4 , were analyzed in a Chinese Han population with 941 cases and 562 controls. Only rs3807989 showed significant association with AF ( P adj =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 ( P adj =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 ( P adj =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, KCNH 2, and HCN 4 and sodium channels Nav1.5 and Nav1.8, CAV 1 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 .