Abstract 16519: A Common Variant at the 16q22 Atrial Fibrillation Risk Locus is Unexpectedly Associated with Reduced Left Atrial Size
Introduction: The common single nucleotide polymorphism (SNP) rs7193343 on chromosome 16q22 (near the zinc finger homeobox 3 (ZFHX3) gene) has consistently been associated with lone and typical AF. However, the mechanism by which rs7193343 contributes to the development of AF remains unknown. Here, we tested the hypothesis that there is an association between rs7193343 and atrial structural remodeling as measured by left atrial (LA) size.
Methods: Three hundred seventeen patients enrolled in the Vanderbilt AF Registry underwent catheter ablation for symptomatic AF between 2004 and 2011. DNA samples were genotyped at rs7193343. LA size (diameter of the AP dimension) was measured prior to initial ablation by cardiac MRI (n=217) or transthoracic echocardiogram (n=100). Linear regression of LA size as a function of rs7193343 genotype was performed adjusting for age, gender, height, body mass index (BMI), time since AF diagnosis, LVEF, lone AF, non-paroxysmal AF, hypertension, CAD, CHF, and history of CABG.
Results: The final cohort consisted of 301 patients (excluded: prior LA ablation (8), prior valve surgery (8)). The minor allele (T) frequency was 22.4%. The rs7193343 T allele was associated with a graded allelic reduction in LA size (CC median 40 mm interquartile range [IQR 34-46]; CT 36.5 mm [IQR 32- 43]; TT 30.5 mm [IQR 27-35]; P=0.0001, Kruskal-Wallis rank sum test). In multivariable analysis using an additive genetic model, heterozygous risk allele carriers demonstrated a 1.4 mm reduction (β=-1.42, standard error [SE] 0.94, P=0.13) and homozygous risk allele carriers a 5.7 mm reduction (β=-5.7, SE 2.3, P=0.016) in LA size. The association remained significant when analyzed in the MRI-only subgroup (P=0.029).
Conclusions: Despite the recognized association between AF and adverse structural remodeling manifest usually by increased LA size, the common AF risk allele at 16q22 confers a reduction in LA size in patients with AF that persists after multivariable adjustment for known predictors of LA size. Defining the etiology of this unexpected association of LA size and rs7193343 will provide important insight into underlying AF mechanisms.
- © 2012 by American Heart Association, Inc.