title: Common Variants in the TBX5 Gene Associated with Atrial Fibrillation in a Chinese Han Population.
abstract: BACKGROUND
  PR interval variations have recently been associated with an increased risk of long-term atrial fibrillation (AF), heart block and all-cause mortality. Genome-wide association studies have linked the PR interval with several common variants in the TBX5 gene. Several variants in the TBX5 gene, including rs7312625 and rs883079, have been associated with AF. The purpose of this study was to determine the association of single-nucleotide polymorphisms (SNPs) in the TBX5 gene, rs7312625 and rs883079, with AF in Chinese Han patients.
  
  
  RESULTS
  In this case-control association study, large cohorts of AF patients (n = 1132) and controls (n = 1206) were recruited from different hospitals. The genotyping was performed using a Rotor-Gene TM 6000 high-resolution melt system. Rs7312625, rs3825214 and rs883079 were analyzed. We found that SNP 3825214 was significantly associated with AF (P-obs = 0.002, odds ratio [OR] = 0.82), and lone AF (P-obs = 6.77x10-5, odds ratio [OR] = 0.71). SNP rs7312625 was significantly associated with lone AF (P-obs = 0.015, odds ratio [OR] = 1.27), although its association with AF was not significant. No significant association of SNP rs883079 with AF or lone AF was observed. Thus, we analyzed the interaction among these three loci. We demonstrated significant interaction among rs3825214, rs7312625 and rs883079. Four-locus risk alleles showed the highest odds ratio in combined rs3825214 and rs7312625 (P-obs<0.0001, odds ratio [OR] = 2.21). Six-locus risk alleles showed the highest odds ratio in combined rs3825214, rs7312625 and rs 883079(P-obs<0.0001, odds ratio [OR] = 2.35). Significance was established with the trend test (P<0.0001).
  
  
  CONCLUSIONS
  For the first time, we report the strong association of SNP rs3825214 in the TBX5 gene with AF and lone AF in a Chinese Han population. Rs7312625 was significantly associated with lone AF, and snp-snp interaction increased the risk of atrial fibrillation. Our data might provide new insights into understanding AF pathogenesis and designing novel genetic therapies for AF patients.
authors.affiliation: First Affiliated Hospital of Dalian Medical University, Dalian, China.
authors.forename: Rongfeng
authors.initials: R
authors.lastname: Zhang
authors.affiliation: First Affiliated Hospital of Dalian Medical University, Dalian, China.
authors.forename: Xiaochen
authors.initials: X
authors.lastname: Tian
authors.affiliation: First Affiliated Hospital of Dalian Medical University, Dalian, China.
authors.forename: Lianjun
authors.initials: L
authors.lastname: Gao
authors.affiliation: First Affiliated Hospital of Dalian Medical University, Dalian, China.
authors.forename: Huihua
authors.initials: H
authors.lastname: Li
authors.affiliation: First Affiliated Hospital of Dalian Medical University, Dalian, China.
authors.forename: Xiaomeng
authors.initials: X
authors.lastname: Yin
authors.affiliation: First Affiliated Hospital of Dalian Medical University, Dalian, China.
authors.forename: Yingxue
authors.initials: Y
authors.lastname: Dong
authors.affiliation: First Affiliated Hospital of Dalian Medical University, Dalian, China.
authors.forename: Yanzong
authors.initials: Y
authors.lastname: Yang
authors.affiliation: First Affiliated Hospital of Dalian Medical University, Dalian, China.
authors.forename: Yunlong
authors.initials: Y
authors.lastname: Xia
mesh_terms: D000328:Adult; D000368:Aged; D000483:Alleles; D044466:Asian People / Q000235:genetics*; D001281:Atrial Fibrillation / Q000235:genetics* / Q000473:pathology; D016022:Case-Control Studies; D002681:China; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D012306:Risk; D020825:T-Box Domain Proteins / Q000235:genetics*
chemical_list: D020825:T-Box Domain Proteins; C103172:T-box transcription factor 5