title: Characterization of SMAD3 Gene Variants for Possible Roles in Ventricular Septal Defects and Other Congenital Heart Diseases.
abstract: BACKGROUND
  Nodal/TGF signaling pathway has an important effect at early stages of differentiation of human embryonic stem cells in directing them to develop into different embryonic lineages. SMAD3 is a key intracellular messenger regulating factor in the Nodal/TGF signaling pathway, playing important roles in embryonic and, particularly, cardiovascular system development. The aim of this work was to find evidence on whether SMAD3 variations might be associated with ventricular septal defects (VSD) or other congenital heart diseases (CHD).
  
  
  METHODS
  We sequenced the SMAD3 gene for 372 Chinese Han CHD patients including 176 VSD patients and evaluated SNP rs2289263, which is located before the 5'UTR sequence of the gene. The statistical analyses were conducted using Chi-Square Tests as implemented in SPSS (version 13.0). The Hardy-Weinberg equilibrium test of the population was carried out using the online software OEGE.
  
  
  RESULTS
  Three heterozygous variants in SMAD3 gene, rs2289263, rs35874463 and rs17228212, were identified. Statistical analyses showed that the rs2289263 variant located before the 5'UTR sequence of SMAD3 gene was associated with the risk of VSD (P value=0.013 <0.05).
  
  
  CONCLUSIONS
  The SNP rs2289263 in the SMAD3 gene is associated with VSD in Chinese Han populations.
authors.affiliation: Genomics Research Center (one of the State-Province Key Laboratory of Biopharmaceutical Engineering, China), Harbin Medical University, Harbin, China.
authors.forename: Fei-Feng
authors.initials: FF
authors.lastname: Li
authors.affiliation: Intensive Care Unit, The Second Affiliated Hospital of Harbin Medical University, Harbin, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Zhou
authors.affiliation: Genomics Research Center (one of the State-Province Key Laboratory of Biopharmaceutical Engineering, China), Harbin Medical University, Harbin, China.
authors.forename: Dan-Dan
authors.initials: DD
authors.lastname: Zhao
authors.affiliation: Department of Colorectal Surgery, the Second Affiliated Hospital of Harbin Medical University, Harbin, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Yan
authors.affiliation: Genomics Research Center (one of the State-Province Key Laboratory of Biopharmaceutical Engineering, China), Harbin Medical University, Harbin, China.
authors.forename: Xia
authors.initials: X
authors.lastname: Li
authors.affiliation: Genomics Research Center (one of the State-Province Key Laboratory of Biopharmaceutical Engineering, China), Harbin Medical University, Harbin, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Han
authors.affiliation: Daqing People's Hospital, Daqing, China.
authors.forename: Xian-Shu
authors.initials: XS
authors.lastname: Li
authors.affiliation: Department of Colorectal Surgery, the Second Affiliated Hospital of Harbin Medical University, Harbin, China.
authors.forename: Gui-Yu
authors.initials: GY
authors.lastname: Wang
authors.affiliation: Intensive Care Unit, The Second Affiliated Hospital of Harbin Medical University, Harbin, China.
authors.forename: Kai-Jiang
authors.initials: KJ
authors.lastname: Yu
authors.affiliation: Genomics Research Center (one of the State-Province Key Laboratory of Biopharmaceutical Engineering, China), Harbin Medical University, Harbin, China; Department of Microbiology, Immunology and Infectious Diseases, University of Calgary, Calgary, Canada.
authors.forename: Shu-Lin
authors.initials: SL
authors.lastname: Liu
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D044466:Asian People / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D002681:China; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006321:Heart / Q000196:embryology*; D006345:Heart Septal Defects, Ventricular / Q000235:genetics*; D006801:Humans; D007223:Infant; D008297:Male; D008875:Middle Aged; D055457:Nodal Protein / Q000378:metabolism; D020641:Polymorphism, Single Nucleotide; D015398:Signal Transduction / Q000235:genetics; D051900:Smad3 Protein / Q000235:genetics*; D055815:Young Adult
chemical_list: C526007:NODAL protein, human; D055457:Nodal Protein; C497790:SMAD3 protein, human; D051900:Smad3 Protein