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

• Published in: PloS one 2015-11, Vol.10 (11), p.e0142666-e0142666
• Main Authors: Li, Fei-Feng, Han, Ying, Shi, Shuai, Li, Xia, Zhu, Xi-Dong, Zhou, Jing, Shao, Qing-Liang, Li, Xue-Qi, Liu, Shu-Lin
• Format: Article
• Language: English
• Subjects: 3' Untranslated regions; Abnormalities; Adolescent; Adult; Analysis; Apoptosis; Binding sites; Cardiology; Cardiovascular diseases; Cell Differentiation - genetics; Child; Child, Preschool; Congenital diseases; Congenital heart defects; Cooperation; Coronary artery disease; Epigenetics; Female; Gene expression; Genetic abnormalities; Genetic aspects; Genetic Association Studies; Genetic diversity; Genetic Predisposition to Disease; Genetic variation; Genomics; Health aspects; Heart; Heart Defects, Congenital - genetics; Heart diseases; Heterozygosity; Homeobox; Homeodomain Proteins - genetics; Hospitals; Humans; Identification and classification; Infant; Laboratories; Male; MicroRNAs; Middle Aged; Morphogenesis; MSX1 Transcription Factor - genetics; Msx2 protein; Muscles; Mutation; Polymorphism, Single Nucleotide; Population (statistical); Risk factors; Signal transduction; Single-nucleotide polymorphism; Statistical analysis; Statistical tests; Statistics; Stem cells; Transcription; Transcription (Genetics); Transcription factors; Variation; Young Adult
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0142666

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