Association between 4q25 variants, risk of atrial fibrillation and echocardiographic parameters

Atrial fibrillation (AF), the most common type of arrhythmia, has a heritable component. Variants at locus 4q25 are best associated with the risk of AF development in genome-wide association studies. Left atrial volume is an independent predictor of recurrence of AF after successful sinus rhythm restoration. The aim of our study was to investigate potential association between genetic variants at 4q25 locus and the risk of AF and echocardiographic parameters. We included 241 AF patients and 119 control individuals into the study. Left ventricle ejection fraction (LVEF, %) and left atrial volume index (LAVI, ml/m²) were assessed by transthoracic echocardiography during outpatient visits. We selected five 4q25 genetic variants (rs6825911, rs1126483, rs10004516, rs6838973, rs2200733) for the analysis. Variant rs6838973 was found to be associated with reduced risk of AF in additive (CCTT) and dominant (CC vs. CT+TT) models of inheritance. On the other hand, additive (CC<CT<TT) and dominant (CC vs. CT+TT) models of rs2200733 were associated with greater risk of AF. The same variations were found to be associated with age of AF onset. Median LAVI was 39.0 ml/m² (IQR = 10.0) and median LVEF was 56.0% (IQR = 13.0). Statistically significant association was observed only between LAVI and variant rs1126483 in the dominant model of inheritance (median LAVI in CC vs. CT+TT – 38 ml/m² vs. 40 ml/m², U = 1602.5, p = 0.032). No significant association was found for LVEF and the analysed genotypes.