Characterization of SMAD3 Gene Variants for Possible Roles in Ventricular Septal Defects and Other Congenital Heart Diseases

Fei-Feng Li; Jing Zhou; Dan-Dan Zhao; Peng Yan; Xia Li; Ying Han; Xian-Shu Li; Gui-Yu Wang; Kai-Jiang Yu; Shu-Lin Liu

doi:10.1371/journal.pone.0131542

Characterization of SMAD3 Gene Variants for Possible Roles in Ventricular Septal Defects and Other Congenital Heart Diseases

PLoS One. 2015 Jun 25;10(6):e0131542. doi: 10.1371/journal.pone.0131542. eCollection 2015.

Authors

Fei-Feng Li¹, Jing Zhou², Dan-Dan Zhao¹, Peng Yan³, Xia Li¹, Ying Han¹, Xian-Shu Li⁴, Gui-Yu Wang³, Kai-Jiang Yu², Shu-Lin Liu⁵

Affiliations

¹ Genomics Research Center (one of the State-Province Key Laboratory of Biopharmaceutical Engineering, China), Harbin Medical University, Harbin, China.
² Intensive Care Unit, The Second Affiliated Hospital of Harbin Medical University, Harbin, China.
³ Department of Colorectal Surgery, the Second Affiliated Hospital of Harbin Medical University, Harbin, China.
⁴ Daqing People's Hospital, Daqing, China.
⁵ 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.

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adolescent
Adult
Aged
Asian People / genetics
Child
Child, Preschool
China
Female
Gene Frequency / genetics
Genetic Association Studies
Genetic Predisposition to Disease
Heart / embryology*
Heart Septal Defects, Ventricular / genetics*
Humans
Infant
Male
Middle Aged
Nodal Protein / metabolism
Polymorphism, Single Nucleotide
Signal Transduction / genetics
Smad3 Protein / genetics*
Young Adult

Substances

NODAL protein, human
Nodal Protein
SMAD3 protein, human
Smad3 Protein

Grants and funding

This work was supported by a grant from Heilongjiang Innovation Research Foundation for Graduate Studies (YJSCX2014-10HYD), a grant from the Heilongjiang Provincial Educational Department (12541431), a grant from Pharmacy College of Harbin Medical University to FFL; and grants of National Natural Science Foundation of China (NSFC81271786, 81110378, 30970119, 81030029) to SLL. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.