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.
Highlights
Atrial fibrillation (AF) is the most prevalent sustained arrhythmia in clinical practice characterized by uncoordinated atrial activation
SNP, single nucleotide polymorphism; AF, atrial fibrillation; MAF, minor allele frequency; PHWE, P values for Hardy–Weinberg equilibrium tests in control groups; Odds ratios (ORs) odds ratio; confidence intervals (CIs) confidence interval. aIndividuals homozygous for the minor allele/heterozygous/homozygous for the major allele. bOR (95%CI) and P values were derived from logistic regression analysis in the additive model adjusting for age, gender, hypertension, diabetes and coronary artery disease. cMultiple comparisons P values for false discovery rate. doi:10.1371/journal.pone.0101318.t002
Considered as common risk factors for AF, hypertension, diabetes, and coronary artery disease (CAD) were more prevalent in cases than controls (P,0.05)
Summary
Atrial fibrillation (AF) is the most prevalent sustained arrhythmia in clinical practice characterized by uncoordinated atrial activation. Epidemiologic studies have shown that first-degree relatives of AF patients were 1.77-fold to 4.67-fold more likely to have AF than the general population, and offspring with one parent suffered from AF had approximately a 2-fold increase in the risk of developing AF [11,12]. These facts indicate that predisposing genetic factors may affect AF susceptibility. Lots of genetic studies of AF were performed by applying several techniques such as linkage analysis, candidate gene resequencing and association studies. We aimed to explore the associations between single nucleotide polymorphisms (SNPs) of ZFHX3 and the risk of AF in a Chinese Han population
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
