DNA Methylation Levels of the TBX5 Gene Promoter Are Associated with Congenital Septal Defects in Mexican Paediatric Patients

• Published in: Biology (Basel, Switzerland) Vol. 11; no. 1; p. 96
• Main Authors: García-Flores, Esbeidy, Rodríguez-Pérez, José Manuel, Borgonio-Cuadra, Verónica Marusa, Vargas-Alarcón, Gilberto, Calderón-Colmenero, Juan, Sandoval, Juan Pablo, García-Montes, José Antonio, Espinoza-Gutiérrez, Víctor Manuel, Reyes-García, Juan Gerardo, Cazarín-Santos, Benny Giovanni, Miranda-Duarte, Antonio, Gamboa-Domínguez, Armando, Pérez-Hernández, Nonanzit
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 08-01-2022; MDPI
• Subjects: Congenital diseases; congenital septal defects; CpG islands; Deoxyribonucleic acid; DNA; DNA methylation; Environmental factors; epigenetic markers; Epigenetics; Genes; Heart; Patients; Pediatrics; Pulmonary arteries; Pulmonary hypertension; Software; Statistical analysis; TBX5 gene; Thermal cycling; Transcription factors; transcriptional factors; United States > US; Mexico; Germany; TBX5 gene; DNA methylation; congenital septal defects; transcriptional factors; epigenetic markers
• ISSN: 2079-7737; 2079-7737
• DOI: 10.3390/biology11010096

The
gene regulates morphological changes during heart development, and it has been associated with epigenetic abnormalities observed in congenital heart defects (CHD). The aim of this research was to evaluate the association between DNA methylation levels of the
gene promoter and congenital septal defects. DNA methylation levels of six CpG sites in the
gene promoter were evaluated using pyrosequencing analysis in 35 patients with congenital septal defects and 48 controls. Average methylation levels were higher in individuals with congenital septal defects than in the controls (
< 0.004). In five CpG sites, we also found higher methylation levels in patients than in the controls (
< 0.05). High methylation levels were associated with congenital septal defects (OR = 3.91; 95% CI = 1.02-14.8;
= 0.045). The analysis of Receiver Operating Characteristic (ROC) showed that the methylation levels of the
gene could be used as a risk marker for congenital septal defects (AUC = 0.68, 95% CI = 0.56-0.80;
= 0.004). Finally, an analysis of environmental factors indicated that maternal infections increased the risk (OR = 2.90; 95% CI = 1.01-8.33;
= 0.048) of congenital septal defects. Our data suggest that a high DNA methylation of the
gene could be associated with congenital septal defects.