Association of functional variant in GDF1 promoter with risk of congenital heart disease and its regulation by Nkx2.5

GDF1 plays an important role in left-right patterning and genetic mutations in the coding region of GDF1 are associated with congenital heart disease (CHD). However, the genetic variation in the promoter of GDF1 with sporadic CHD and its expression regulation is little known. The association of the genetic variation in GDF1 promoter with CHD was examined in two case-control studies, including 1084 cases and 1198 controls in the first study and 582 cases and 615 controls in the second study. We identified one single nucleotide polymorphism (SNP) rs181317402 and two novel genetic mutations located in the promoter region of GDF1. Analysis of combined samples revealed a significant association in genotype and allele frequencies of rs181317402 T/G polymorphism between CHD cases in overall or ventricular septal defects or Tetralogy of Fallot and the control group. Rs181317402 allele G polymorphism was significantly associated with a decreased risk of CHD. Furthermore, luciferase assay, chromatin immunoprecipitation and DNA pulldown assay indicated that Nkx2.5 transactivated the expression of GDF1 by binding to the promoter of GDF1. Luciferase activity assay showed that rs181317402 allele G significantly increased the basal and Nkx2.5-mediated activity of GDF1 promoter, while the two genetic mutations had the opposite effect. Rs181317402 TG genotype was associated with significantly increased mRNA level of GDF1 compared with TT genotype in 18 CHD individuals. Our results demonstrate...
Source: Clinical Science - Category: Biomedical Science Authors: Tags: PublishAheadOfPrint Source Type: research

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Abstract CITED2 is a cardiac transcription factor that plays a critical role in cardiac development. Gene mutations in CITED2 lead to a series of cardiac malformations and congenital heart defects (CHD). Congenital heart disease generally refers to defects in the heart's structure or function and often seen in many forms such as ventricular septal defects (VSDs), atrial septal defects (ASDs), and tetralogy of Fallot (TOF). However, the mechanisms involved in these mutations are poorly understood. The aim of the present study was to evaluate the mutations of the CITED2 gene in pediatric patients with congenital hea...
Source: Applied Biochemistry and Biotechnology - Category: Biochemistry Authors: Tags: Appl Biochem Biotechnol Source Type: research
ille Iolascon Mario Capasso In the past years, genome wide association studies (GWAS) have provided evidence that inter-individual susceptibility to diverse pathological conditions can reveal a common genetic architecture. Through the analysis of congenital heart disease (CHD) and neuroblastoma (NB) GWAS data, we aimed to dissect the genetic susceptibility shared between these conditions, which are known to arise from neural crest cell (NCC) migration or development abnormalities, via identification and functional characterization of common regions of association. Two loci (2q35 and 3q25.32) harbor single nucleotide ...
Source: Genes - Category: Genetics & Stem Cells Authors: Tags: Article Source Type: research
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Source: Journal of Thoracic Imaging - Category: Radiology Tags: Web Exclusive Content: Pictorial Essays Source Type: research
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Source: The American Journal of Cardiology - Category: Cardiology Authors: Source Type: research
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Source: Journal of Nuclear Cardiology - Category: Nuclear Medicine Source Type: research
Ventricular septal defect (VSD) is a fatal congenital heart disease showing severe consequence in affected infants, to which early diagnosis plays an important role, particularly through genetic variants. Existing panel-based approaches of variants mining suffer from shortage of large panels, costly of sequencing and missing of rare variants. Although a trio-based method alleviates these limitations to some extent, it is agnostic to novel mutations and computational intensive. Considering these limitations, we are studying a novel variants mining algorithm from trio-based sequencing data and apply it on a VSD trio to ident...
Source: Frontiers in Genetics - Category: Genetics & Stem Cells Source Type: research
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Source: Archives of Cardiovascular Diseases Supplements - Category: Cardiology Source Type: research
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Source: Journal of Cardiothoracic and Vascular Anesthesia - Category: Anesthesiology Authors: Tags: Original Article Source Type: research
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Source: Revista da Associacao Medica Brasileira - Category: General Medicine Source Type: research
Pulmonary atresia with ventricular septal defect and major aortopulmonary collateral arteries (PA/VSD/MAPCAs) is a rare and heterogeneous form of congenital heart disease. Despite improvements in the surgical management of this disease, there is still an ongoing controversy regarding the optimal treatment. Part II of this paper will focus on the surgical results of unifocalization and the need and techniques used for unifocalization revision at Stanford University.
Source: Operative Techniques in Cardiac and Thoracic Surgery - Category: Cardiovascular & Thoracic Surgery Authors: Tags: Congenital Source Type: research
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