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A functional polymorphism C-509T in TGF?-1 promoter contributes to susceptibility and prognosis of lone atrial fibrillation in Chinese population.

ABSTRACT: Transforming growth factor-?1 (TGF-?1) is an important mediator of atrial fibrosis and atrial fibrillation (AF). But the involved genetic mechanism is unknown. Herein, the TGF-?1 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-?1CC 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-?1 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-?1 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-?1 in AF.

SUBMITTER: Cao H

PROVIDER: S-EPMC4234495 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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A functional polymorphism C-509T in TGFβ-1 promoter contributes to susceptibility and prognosis of lone atrial fibrillation in Chinese population.

Cao Hailong H Zhou Qing Q Lan Rongfang R Røe Oluf Dimitri OD Chen Xin X Chen Yijiang Y Wang Dongjin D

PloS one 20141117 11

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) = ...[more]

PMID: 25402477

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Project description:Abstract Background Epicardial adipose tissue (EAT) has been considered as one of the probable triggers of atrial fibrillation (AF). CT‐rediomics is a perspective noninvasive method of assessment of EAT. We evaluate the radiomic phenotype of EAT in patients with lone AF in the prognosis of AF recurrence after catheter ablation. Methods A total of 43 patients with lone AF referred for CA and 20 out‐hospital patients without arrhythmia underwent multidetector computed tomography coronary angiography. Segmentation of EAT and extraction radiomic features were performed on calcium scoring series using by 3D‐Slicer. Clinical follow‐up was performed for 12 months period after the CA. Results EAT in patients with lone AF had a distinct radiomic phenotype. Thus, 45 of 93 calculated radiomic features, volume and attenuation of EAT were significantly different between patients with lone AF and persons without any arrhythmia. In addition, 17 radiomic features were significantly different in subgroups with and without AF recurrence. Multivariate regression analysis demonstrated that only gray level nonuniformity normalized (GLSZM) was an independent predictor of AF recurrence (OR 1.0027, 95%CI 1.0009–1.0044, p = 0.002). ROC analysis data showed that GLSZM >1227.4 indicates high probability of AF recurrence during 12 months (sensitivity 89.4%, specificity 70.8%, AUC: 0.809; p = 0.001). Conclusion The radiomic parameter GLSZM is associated with late AF recurrence after CA in patients with lone AF. In current study GLSZM was a stronger predictor of lone AF recurrence in multivariate analysis comparing with other established risk factors and EAT volume and attenuation. This study is a step forward towards the application of radiomic analisys for study the role of epicardial adipose tissue in the occurrence of AF recurrence after ablation. The results are significantly important due to the fact it was shown that the radiomic parameter GLSZM is associated with late AF recurrence after CA in patients without structural changes of myocardium. Moreover, GLSZM was the stronger predictor of isolated AF recurrence in multivariate analysis comparing with other established risk factors and EAT volume and attenuation.

Project description:RationaleAtrial fibrillation (AF) is encountered rarely in pregnancy. Management of maternal AF is challenging as it poses a threat to both maternal and fetal well-being.Patient concernsWe report a case of a 35 weeks pregnant woman who presented in emergency with sudden-onset palpitations and mild shortness of breath with no personal/family history of cardiac diseases.DiagnosesPatient's pulse was irregularly irregular with an average rate of 179 beats per minute. The obstetric examination was normal.DiagnosisHigh-sensitive cardiac troponin T (hs-cTnT) was elevated. The 12 lead electrocardiogram (ECG) confirmed AF. The obstetric ultrasound, electronic fetal heart rate (EFHR) trace, and maternal echocardiography were normal.InterventionsThe patient was admitted under joint cardiology and obstetric care and monitored with continuous telemetry. She was commenced on a therapeutic dose of low-molecular weight heparin (LMWH) and intravenous fluid. She received a single 200 Joule synchronized direct current (DC) shock under general anesthesia in operation theater, which reverted the rhythm back to normal. EFHR monitoring was normal pre- and post-DC cardioversion. We acknowledge the unwise use of therapeutic dose of LMWH before DC cardioversion (DCCV) because of a potential need for emergency cesarean delivery for maternal and/or fetal compromise.OutcomeThe patient remained well and in sinus rhythm after cardioversion. She was discharged home the following day on Flecainide (anti-arrhythmic) and therapeutic dose of low molecular weight heparin (LMWH) and followed up in outpatient clinics frequently. She had a baby at term and received prophylactic LMWH for 10 days post-cesarean. She was discharged from cardiology clinic when she was 10 weeks postnatal, and Flecainide was discontinued.LessonsWe are reporting this case because of the rarity of the condition and successful use of DCCV for treating maternal AF. High-sensitive cardiac troponin T (hs-cTnT) level is a useful laboratory indicator to gauge the severity of AF in pregnancy. We emphasize to make the arrangements for EFHR monitoring and potential cesarean delivery and advocate cautious use of thromboprophylaxis while planning for electrical cardioversion (ECV) for maternal AF.

Dataset Information

A functional polymorphism C-509T in TGF?-1 promoter contributes to susceptibility and prognosis of lone atrial fibrillation in Chinese population.

Publications

A functional polymorphism C-509T in TGFβ-1 promoter contributes to susceptibility and prognosis of lone atrial fibrillation in Chinese population.

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