Using a linear regression model and adapting a resampling inference, a decrease in longitudinal QTc variance was found to associate with SNPs near KCNH2 (rs10240738) and KCNJ2 (rs8079702) when adjusted for patient age, gender, AF type, and average QTc.
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.
Various genes involved in Ca<sup>2+</sup> handling or gap junction formation ( Ryr2, Jph2, Gja5), potassium channels ( Kcnh2, Kcnk3), and genes implicated in atrial fibrillation ( Tbx5) were part of this ETV1-driven gene regulatory network.
After the age of 60 years, patients with LQT2 had significantly lower risk of AF compared with genotype-negative controls (hazard ratio=0.07; 95% CI, 0.01-0.53, <i>P</i>=0.011).
In overall random-effects meta-analyses, association with AF was observed for both SNPs on chromosomes 4q25 [odds ratio (OR), 1.67; 95% CI, 1.50-1.86, P=2×10(-21)] and 16q22 (OR, 1.21; 95% CI, 1.13-1.29, P=1×10(-8)) from genome-wide studies, but not the SNP in KCNH2 from candidate gene studies (P=0.15).
A benign variety of the disease has been observed in children with atrial fibrillation and a KCNH2-V141M mutation, and recently a mutation in the cardiac Cl/HCO<sub>3</sub> exchanger AE3 was found to cause SQTS.
In a pair-matched, hospital-based case control study (297 vs 297) conducted in Chinese Hans, we investigated 4 tagging single nucleotide polymorphisms (tSNPs), rs1805120, rs1036145, rs3807375, and rs2968857 in the KCNH2 gene, and determined their association with AF acquired from structural heart diseases.
To potentially model aspects of AF and unravel PITX2-regulated downstream genes for drug target discovery, we here report the generation of integration-free PITX2-deficient hiPS cell lines.
Recent genome-wide association studies have identified 3 loci, on chromosomes 4q25 (near PITX2), 16q22 (in ZFHX3), and 1q21 (in KCNN3), that associate with either typical or lone AF.