Novel and functional variants within the TBX18 gene promoter in ventricular septal defects

Congenital heart disease (CHD) is the most common birth defect in humans. Genetic causes for CHD remain largely unknown. T-box transcription factor 18 (TBX18) gene is expressed in the developing heart, including myocardium of the left ventricle and interventricular septum. Epicardial cells expressin...

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Bibliographic Details
Published in:Molecular and cellular biochemistry 2013-10, Vol.382 (1-2), p.121-126
Main Authors: Ma, Liming, Li, Jianjun, Liu, Yumei, Pang, Shuchao, Huang, Wenhui, Yan, Bo
Format: Article
Language:English
Subjects:
Adolescent
Adult
Base Sequence
Biochemistry
Biomedical and Life Sciences
Birth defects
Cardiac muscle
Cardiology
Cardiovascular disease
Cardiovascular diseases
Child
Child, Preschool
Deoxyribonucleic acid
DNA
Female
Genes
Genetic aspects
Genetic transcription
Genetics
Heart diseases
Heart Septal Defects, Ventricular - genetics
Humans
Infant
Life Sciences
Male
Medical Biochemistry
Middle Aged
Molecular Sequence Data
Oncology
Polymorphism, Single Nucleotide - genetics
Promoter Regions, Genetic
T-Box Domain Proteins - genetics
Transcription, Genetic
Ventricular septal defects
Young Adult
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Summary:Congenital heart disease (CHD) is the most common birth defect in humans. Genetic causes for CHD remain largely unknown. T-box transcription factor 18 (TBX18) gene is expressed in the developing heart, including myocardium of the left ventricle and interventricular septum. Epicardial cells expressing TBX18 gene contribute to the cardiac fibroblast and smooth muscle cells. We speculated that the DNA sequence variants (DSVs) within TBX18 gene promoter may mediate CHD development by affecting TBX18 levels and the cardiac gene regulatory network. In this study, we genetically and functionally analyzed the TBX18 gene promoter in patients with ventricular septal defects (VSD) ( n  = 326) and ethnic-matched healthy controls ( n  = 327). Three novel heterozygous DSVs (g.85474435del, g.85474418C>T, and g.85473965C>G) and one single nucleotide polymorphism (g.85474871C>T, rs77693245) were identified in VSD patients, but none in the controls. Functional analysis revealed that the DSVs (g.85474871C>T, g.85474435del, and g.85473965C>G) significantly decreased the transcriptional activities of the TBX18 gene promoter. The effect of DSV (g.85474418C>T) on the TBX18 gene promoter was marginal, but not significant. Therefore, the DSVs within the TBX18 gene promoter identified in VSD patients may be involved in the VSD etiology.
ISSN:0300-8177
1573-4919
DOI:10.1007/s11010-013-1725-4