Association between ZFHX3 and PRRX1 Polymorphisms and Atrial Fibrillation Susceptibility from Meta-Analysis

Abstract

Background. Atrial fibrillation (AF) is a common, sustained cardiac arrhythmia. Recent studies have reported an association between ZFHX3/PRRX1 polymorphisms and AF. In this study, a meta-analysis was conducted to confirm these associations. Objective and Methods. The PubMed, Embase, and Wanfang databases were searched, covering all publications before July 20, 2020. Results. Overall, seven articles including 3,674 cases and 8,990 healthy controls for ZFHX3 rs2106261 and 1045 cases and 1407 controls for PRRX1 rs3903239 were included. The odds ratio (OR) (95% confidence interval (CI)) was used to assess the associations. Publication bias was calculated using Egger’s and Begg’s tests. We found that the ZFHX3 rs2106261 polymorphism increased AF risk in Asians (for example, allelic contrast: OR [95% CI]: 1.39 [1.31–1.47], P < 0.001 ). Similarly, strong associations were detected through stratified analysis using source of control and genotype methods (for example, allelic contrast: OR [95% CI]: 1.51 [1.38–1.64], P < 0.001 for HB; OR [95% CI]: 1.31 [1.21–1.41], P < 0.001 for PB; OR [95% CI]: 1.55 [1.33–1.80], P < 0.001 for TaqMan; and OR [95% CI]: 1.31 [1.21–1.41], P < 0.001 for high-resolution melt). In contrast, an inverse relationship was observed between the PRRX1 rs3903239 polymorphism and AF risk (C-allele vs. T-allele: OR [95% CI]: 0.83 [0.77–0.99], P = 0.036 ; CT vs. TT: OR [95% CI]: 0.79 [0.67–0.94], P = 0.006 ). No obvious evidence of publication bias was observed. Conclusions. In summary, our study suggests that the ZFHX3 rs2106261 and PRRX1 rs3903239 polymorphisms are associated with AF risk, and larger case-controls must be carried out to confirm the abovementioned conclusions.

A novel PRRX1 loss-of-function variation contributing to familial atrial fibrillation and congenital patent ductus arteriosus

“…Recently, multiple genome-wide association studies and a meta-analysis consistently revealed that a common single nucleotide polymorphism (rs3903239) about 63 kb upstream of the PRRX1 gene, a top genetic variation at the locus of AF on chromosome 1q24, was associated with significantly increased risk of AF in both Europeans and Asians ( Tucker et al , 2017 ; Wu et al , 2021 ). Functional analyses unveiled that this variant diminished the transcriptional activity of the promoter of PRRX1 , resulting in reduced expression of PRRX1 in human left atrial tissue ( Tucker et al , 2017 ).…”

Identification of Novel Genes Associated with Atrial Fibrillation and Development of Atrial Fibrillation Predictive Models by Incorporating Polygenic Risk Scores and PheWAS-Derived Risk Factors

“…ZFHX3 (Zinc Finger Homeobox 3) has been proved an associated gene to AF. 31 Zaw, et al suggested that ZFHX3 polymorphism was a risk marker for AF and AF-related phenotypes. 32 The potential mechanism of the association between ZFHX3 and AF was examined by knock down ZFHX3 in atrial myocytes, and the results demonstrated the dysregulated calcium homeostasis and increased atrial arrhythmogenesis, which might contribute to the occurrence of AF.…”