Characterization of Transcriptional Repressor Gene MSX1 Variations for Possible Associations with Congenital Heart Diseases

Fei-Feng Li; Ying Han; Shuai Shi; Xia Li; Xi-Dong Zhu; Jing Zhou; Qing-Liang Shao; Xue-Qi Li; Shu-Lin Liu

doi:10.1371/journal.pone.0142666

Characterization of Transcriptional Repressor Gene MSX1 Variations for Possible Associations with Congenital Heart Diseases

PLoS One. 2015 Nov 10;10(11):e0142666. doi: 10.1371/journal.pone.0142666. eCollection 2015.

Authors

Fei-Feng Li^{1

2}, Ying Han³, Shuai Shi³, Xia Li¹, Xi-Dong Zhu⁴, Jing Zhou⁵, Qing-Liang Shao⁶, Xue-Qi Li³, Shu-Lin Liu^{1

2

7}

Affiliations

¹ Genomics Research Center (one of the State-Province Key Laboratory of Biopharmaceutical Engineering, China), Harbin Medical University, Harbin, China.
² Translational Medicine Research and Cooperation Center of Northern China, Heilongjiang Academy of Medical Sciences, Heilongjiang, China.
³ Department of Cardiology, the Fourth Affiliated Hospital of Harbin Medical University, Harbin, China.
⁴ Department of Neurology, the Second Affiliated Hospital of Harbin Medical University, Harbin, China.
⁵ Intensive care unit, the Second Affiliated Hospital of Harbin Medical University, Harbin, China.
⁶ Department of Neonatalogy, the Second Affiliated Hospital of Harbin Medical University, Harbin, China.
⁷ Department of Microbiology, Immunology and Infectious Diseases, University of Calgary, Calgary, Canada.

Abstract

Background: The human heart consists of several cell types with distinct lineage origins. Interactions between these cardiac progenitors are very important for heart formation. The muscle segment homeobox gene family plays a key role in the cell morphogenesis and growth, controlled cellular proliferation, differentiation, and apoptosis, but the relationships between the genetic abnormalities and CHD phenotypes still remain largely unknown. The aim of this work was to evaluate variations in MSX1 and MSX2 for their possible associations with CHD.

Methods: We sequenced the MSX1 and MSX2 genes for 300 Chinese Han CHD patients and 400 normal controls and identified the variations. The statistical analyses were conducted using Chi-Square Tests as implemented in SPSS (version 19.0). The Hardy-Weinberg equilibrium test of the population was carried out using the online software OEGE.

Results: Six variations rs4647952, rs2048152, rs4242182, rs61739543, rs111542301 and rs3087539 were identified in the MSX2 gene, but the genetic heterozygosity of those SNPs was very low. In contrast, the genetic heterozygosity of two variations rs3821949 near the 5'UTR and rs12532 within 3'UTR of the MSX1 gene was considerably high. Statistical analyses showed that rs3821949 and rs12532 were associated with the risk of CHD (specifically VSD).

Conclusions: The SNPs rs3821949 and rs12532 in the MSX1 gene were associated with CHD in Chinese Han populations.

Publication types

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

MeSH terms

Adolescent
Adult
Cell Differentiation / genetics
Child
Child, Preschool
Female
Genetic Association Studies
Genetic Predisposition to Disease
Heart Defects, Congenital / genetics*
Homeodomain Proteins / genetics
Humans
Infant
MSX1 Transcription Factor / genetics*
Male
Middle Aged
Polymorphism, Single Nucleotide*
Young Adult

Substances

Homeodomain Proteins
MSX1 Transcription Factor
MSX1 protein, human
MSX2 protein

Grants and funding

This work was supported by a grant from Heilongjiang Innovation Research Foundation for Graduate Studies (YJSCX2014-10HYD), 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.