Six single-nucleotide polymorphisms-rs593479 (1q24 in PRRX1), rs1906617 (4q25 near PITX2), rs11773845 (7q31 in CAV1), rs6584555 (10q25 in NEURL), rs6490029 (12q24 in CUX2), and rs12932445 (16q22 in ZFHX3) (P < 1.9 × 10<sup>-5</sup>)-were confirmed as being associated with AF.
CONCLUSIONS The results revealed a significant association between CAV1 gene rs3807989 polymorphism and susceptibility to AF, suggesting that the presence of allelic G might be one of the genetic factors conferring susceptibility to AF.
We identified novel cis-acting associations in atrial tissue between AF risk SNPs and increased expression of PITX2a/b; and decreased expression of CAV1 (an association also seen in peripheral blood), C9orf3 and FANCC.
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.
Genome-wide association studies (GWAS) have identified common variants in nine genomic regions associated with AF (KCNN3, PRRX1, PITX2, WNT8A, CAV1, C9orf3, SYNE2, HCN4 and ZFHX3 genes); however, the genetic variability of these risk variants does not explain the entire genetic susceptibility to AF.
Among GWAS loci for AF, only three were replicated in the Chinese Han population, including SNP rs2106261 (G/A substitution) in ZFHX3, rs2200733 (C/T substitution) near PITX2c, and rs3807989 (A/G substitution) in CAV1.
The SNP rs3807989 in CAV1 gene is not associated with AF or lone AF in our studies, which suggests that the SNP rs3807989 in CAV1 may not be a risk factor for AF in Chinese Han population.
Three SNPs were found to be significantly associated with early-onset lone AF: rs2200733 closest to PITX2 (odds ratio [OR], 1.62; 95% confidence interval [CI], 1.16-2.27; P = 0.004), rs3807989 near to CAV1 (OR 1.35; 95% CI, 1.06-1.72; P = 0.015), and rs11047543 near to SOX5 (OR 1.70; 95% CI, 1.18-2.44; P = 0.004).
We observed correlations between TBX5 and CAV1 and atrial fibrillation (P = 4.0 x 10(-5) and P = 0.00032, respectively), between TBX5 and advanced atrioventricular block (P = 0.0067), and between SCN10A and pacemaker implantation (P = 0.0029).