title: Genetic polymorphisms in ZFHX3 are associated with atrial fibrillation in a Chinese Han population.
abstract: BACKGROUND
  The 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.
  
  
  METHODS
  We 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.
  
  
  RESULTS
  We 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.
  
  
  CONCLUSIONS
  In 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.
authors.affiliation: Department of Cardiology, the First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China.
authors.forename: Yaowu
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Epidemiology and Biostatistics, School of Public Health, Nanjing Medical University, Nanjing, Jiangsu, China.
authors.forename: Bixian
authors.initials: B
authors.lastname: Ni
authors.affiliation: Department of Epidemiology and Biostatistics, School of Public Health, Nanjing Medical University, Nanjing, Jiangsu, China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Lin
authors.affiliation: Department of Cardiology, the First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China.
authors.forename: Xin-guang
authors.initials: XG
authors.lastname: Chen
authors.affiliation: Department of Cardiology, the First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Fang
authors.affiliation: Department of Cardiology, the First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China.
authors.forename: Liyan
authors.initials: L
authors.lastname: Zhao
authors.affiliation: Department of Epidemiology and Biostatistics, School of Public Health, Nanjing Medical University, Nanjing, Jiangsu, China.
authors.forename: Zhibin
authors.initials: Z
authors.lastname: Hu
authors.affiliation: Department of Cardiology, the First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China.
authors.forename: Fengxiang
authors.initials: F
authors.lastname: Zhang
mesh_terms: D000368:Aged; D044466:Asian People; D001281:Atrial Fibrillation / Q000208:ethnology / Q000235:genetics*; D002681:China / Q000208:ethnology; D005260:Female; D020022:Genetic Predisposition to Disease; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D012306:Risk
chemical_list: D018398:Homeodomain Proteins; C071660:ZFHX3 protein, human