title: Novel and functional sequence variants within the TBX2 gene promoter in ventricular septal defects.
abstract: Congenital heart disease (CHD) is the most common birth defects in humans. To date, genetic causes for CHD remain largely unknown. T-box transcription factor 2 (TBX2) gene is expressed in the myocardium of atrioventricular canal, outflow tract and inflow tract and plays a critical role in heart chamber formation. Genomic deletion and duplication of TBX2 gene have been associated with cardiac defects. As TBX2 acts in a dose-dependent manner, we hypothesized that DNA sequence variants (DSVs) within TBX2 gene promoter may mediate CHD development by changing TBX2 levels. In this study, TBX2 gene promoter was genetically analyzed in large cohorts of patients with ventricular septal defect (VSD) (n = 324) and ethnic-matched healthy controls (n = 328). Four novel and heterozygous DSVs, g.59477201C > T, g.59477347G > A, g.59477353delG and g.59477371G > A were identified in VSD patients, but in none of controls. Functional analyses revealed that all of the four DSVs significantly decreased transcriptional activities of TBX2 gene promoter. Therefore, our data suggested that the DSVs within TBX2 gene promoter identified in VSD patients may contribute to VSD etiology.
authors.affiliation: Shandong Provincial Key Laboratory of Cardiac Disease Diagnosis and Treatment, Jining Medical University Affiliated Hospital, Jining Medical University, 79 Guhuai Road, Jining, Shandong 272029, China.
authors.forename: Shuchao
authors.initials: S
authors.lastname: Pang
authors.forename: Yumei
authors.initials: Y
authors.lastname: Liu
authors.forename: Zhongqing
authors.initials: Z
authors.lastname: Zhao
authors.forename: Wenhui
authors.initials: W
authors.lastname: Huang
authors.forename: Dongfeng
authors.initials: D
authors.lastname: Chen
authors.forename: Bo
authors.initials: B
authors.lastname: Yan
mesh_terms: D000293:Adolescent; D000328:Adult; D001483:Base Sequence; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D005260:Female; D006345:Heart Septal Defects, Ventricular / Q000208:ethnology / Q000235:genetics*; D006801:Humans; D007223:Infant; D008297:Male; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic / Q000235:genetics*; D020825:T-Box Domain Proteins / Q000235:genetics*; D055815:Young Adult
chemical_list: C097348:T-Box Domain Protein 2; D020825:T-Box Domain Proteins
keywords: Congenital heart disease; DNA sequence variants; Promoter; TBX2; Ventricular septal defect