Genetic Polymorphisms in ZFHX3 Are Associated with Atrial Fibrillation in a Chinese Han Population

Abstract

BackgroundThe gene zinc finger homeobox 3 (ZFHX3) encodes a transcription factor with cardiac expression and its genetic variants are associated with atrial fibrillation (AF). We aimed to explore the associations between single nucleotide polymorphisms (SNPs) of ZFHX3 and the risk of AF in a Chinese Han population.MethodsWe genotyped eight SNPs, including seven potentially functional SNPs and one previously reported SNP by using the middle-throughput iPLEX Sequenom MassARRAY platform. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated in logistic regression models.ResultsWe enrolled a total of 1,593 Chinese Han origin individuals in the study, including 597 AF patients and 996 non-AF controls. Logistic regression analyses revealed that potentially functional SNPs rs6499600 and rs16971436 were associated with a decreased risk of AF (adjusted OR = 0.73, 95% CI: 0.63–0.86, P = 1.07×10−4; adjusted OR = 0.74, 95% CI: 0.56–0.98, P = 0.039, respectively). In addition, rs2106261 showed a robust association with an increased risk of AF (adjusted OR = 1.71, 95% CI: 1.46–2.00, P = 1.85×10−11). After multiple comparisons, rs16971436 conferred a borderline significant association with the risk of AF. Stratification analysis indicated that the risks of AF were statistically different among subgroups of age for rs2106261, and the effect for rs16971436 was more evident in subgroups of patients with coronary artery disease.ConclusionIn summary, our study investigated the role of genetic variants of ZFHX3 in AF and two SNPs (rs2106261, rs6499600) showed significant associations while rs16971436 conferred a borderline significant association with AF risk in Chinese Han populations. However, further large and functional studies are warranted to confirm our findings.

The Characteristics of Mirna Binding Sites in Mrna of Zfhx3 Gene and Its Orthologs

“…We assume that the polysite binds to miR-1322, so the encoded polyGln of ZFHX3 transcription factor can interact with negatively charged regions of DNA-binding proteins. Another our assumption is that the polyGln variability of ZFHX3 protein is associated with the development of several diseases, but the way it happens remains unknown (Liu et al, 2014;Martin et al, 2014;Chauhan et al, 2016;Hauer et al, 2017 The binding site of miR-11-29856-3p encoded the absolutely conservative heptapeptide TETLLQL, presented in the protein of 55 species of animals (Supplementary table 10). Absolutely conservative heptapeptide LLPHFPMT adjoined the N-terminus of the heptapeptide, and the variable region of the ZFHX3 protein -the C-terminus.…”

“…These include the ZFHX3 gene encoding the transcription factor involved in the regulation of expression of many genes. Disruption in ZFHX3 gene expression was identified in stroke, atherosclerosis and other cardiovascular diseases (Liu et al, 2014;Martin et al, 2014;Chauhan et al, 2016;Hauer et al, 2017). Gene ZFHX3, being a transcription factor, can manifest its function in a variety of ways, and be a cause of different stroke subtypes.…”

Good responders to catheter ablation for long-standing persistent atrial fibrillation: Clinical and genetic characteristics

“…We evaluated top six SNPs that have previously proven to be associated with AF in a European ancestry database and an Asian population [13][14][15]: rs2200733 and PITX2 (rs6843082 and rs17042171) on chromosome 4q25, ZFHX3 (rs7193343 and rs2106261) on chromosome 16q22, and KCNN3 (rs13376333) on chromosome 1q21. We used whole blood samples for the DNA extraction and genetic analyses.…”

A genetic stochastic process model for genome‐wide joint analysis of biomarker dynamics and disease susceptibility with longitudinal data

“…A SNP rs823968 in EPHB1 in modest LD (r 2 = 0.2) with rs9874828 is associated with T2D in a Finnish population (Scott et al, 2007). In addition, rs7185166 is located in ZFHX3, variants in which are reportedly associated with a diverse range of diseases including coronary heart disease (Sun, Zhang, Chen, & Song, 2015), atrial fibrillation (Gudbjartsson et al, 2009;Liu et al, 2014), and stroke (Liu et al, 2014). A recent study has found that a mutation in this gene disrupts circadian locomotor rhythms in mice (Parsons et al, 2015), which may explain its pleiotropic effects on these seemingly unrelated diseases.…”