A functional polymorphism C-509T in TGFβ-1 promoter contributes to susceptibility and prognosis of lone atrial fibrillation in Chinese population.
Transforming growth factor-β1 (TGF-β1) is an important mediator of atrial fibrosis and atrial fibrillation (AF). But the involved genetic mechanism is unknown. Herein, the TGF-β1 C-509 T polymorphism (rs1800469) was genotyped in a case-control study of 840 patients and 845 controls in Chinese population to explore the association between the polymorphism and susceptibility and prognosis of lone AF. As a result, the CT and/or TT genotypes had an increased lone AF risk [adjusted odds ratio (OR) = 1.50 for CT, OR = 3.72 for TT, and OR = 2.15 for CT/TT], compared with the TGF-β1CC genotype. Moreover, patients carrying CT/TT genotypes showed a higher possibility of AF recurrence after catheter ablation, compared with patients carrying CC genotype. In a genotype-phenotype correlation analysis using 24 normal left atrial appendage samples, increasing gradients of atrial TGF-β1 expression levels positively correlated with atrial collagen volume fraction were identified in samples with CC, CT and TT genotypes. The in vitro luciferase assays also showed a higher luciferase activity of the -509 T allele than that of the -509 C allele. In conclusion, the TGF-β1 C-509 T polymorphism is involved in the etiology of lone AF and thus may be a marker for genetic susceptibility to lone AF and predicting prognosis after catheter ablation in Chinese populations. Therefore, we provide new information about treatment strategies and our understanding of TGF-β1 in AF.
Department of Thoracic and Cardiovascular Surgery, the Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China.
Hailong
H
Cao
Department of Thoracic and Cardiovascular Surgery, the Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China.
Qing
Q
Zhou
Department of Cardiology, the Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China.
Rongfang
R
Lan
Department of Thoracic and Cardiovascular Surgery, the First Affiliated Hospital of Nanjing Medical University, Nanjing, China; Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology (NTNU), Trondheim, Norway.
Oluf Dimitri
OD
Røe
Department of Cardiology, the Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China.
Xin
X
Chen
Department of Thoracic and Cardiovascular Surgery, the First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
Yijiang
Y
Chen
Department of Thoracic and Cardiovascular Surgery, the Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China.
Dongjin
D
Wang
D000328:Adult; D000368:Aged; D000483:Alleles; D044466:Asian People / Q000235:genetics*; D001281:Atrial Fibrillation / Q000235:genetics* / Q000401:mortality / Q000473:pathology / Q000628:therapy; D016022:Case-Control Studies; D017115:Catheter Ablation; D002681:China; D005260:Female; D005355:Fibrosis; D005500:Follow-Up Studies; D015870:Gene Expression; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D011401:Promoter Regions, Genetic; D012008:Recurrence; D012307:Risk Factors; D053773:Transforming Growth Factor beta1 / Q000235:genetics*; D016896:Treatment Outcome
C508960:TGFB1 protein, human; D053773:Transforming Growth Factor beta1