Susceptibility to congenital heart defects associated with a polymorphism in TBX2 3' untranslated region in the Han Chinese population.
Pediatr Res
; 85(3): 378-383, 2019 02.
Article
em En
| MEDLINE
| ID: mdl-30262811
ABSTRACT
BACKGROUND:
Tbx2 plays a critical role in determining fates of cardiomyocytes. Little is known about the contribution of TBX2 3' untranslated region (UTR) variants to the risk of congenital heart defect (CHD). Thus, we aimed to determine the association of single-nucleotide polymorphisms (SNPs) in TBX2 3' UTR with CHD susceptibility.METHODS:
We recruited 1285 controls and 1241 CHD children from China. SNPs identification and genotyping were detected using Sanger Sequencing and SNaPshot. Stratified analysis was conducted to explore the association between rs59382073 polymorphism and CHD subtypes. Functional analyses were performed by luciferase assays in HEK-293T and H9c2 cells.RESULTS:
Among five TBX2 3'UTR variants identified, rs59382073 minor allele T carriers had a 1.89-fold increased CHD risk compared to GG genotype (95% CI = 1.48-2.46, P = 4.48 × 10-7). The most probable subtypes were right ventricular outflow tract obstruction, conotruncal, and septal defect. G to T variation decreased luciferase activity in cells. This discrepancy was exaggerated by miR-3940 and miR-708, while their corresponding inhibitors eliminated it.CONCLUSION:
T allele of rs59382073 in TBX2 3'UTR contributed to greater CHD risk in the Han Chinese population. G to T variation created binding sites for miR-3940 and miR-708 to inhibit gene expression.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Predisposição Genética para Doença
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Proteínas com Domínio T
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Polimorfismo de Nucleotídeo Único
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Cardiopatias Congênitas
Tipo de estudo:
Clinical_trials
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Etiology_studies
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Observational_studies
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Prognostic_studies
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Risk_factors_studies
Limite:
Animals
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Child
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Female
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Humans
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Male
País como assunto:
Asia
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article