Epigenetic Evaluation of the TBX20 Gene and Environmental Risk Factors in Mexican Paediatric Patients with Congenital Septal Defects.

The TBX20 gene has a key role during cardiogenesis, and it has been related to epigenetic mechanisms in congenital heart disease (CHD). The purpose of this study was to assess the association between DNA methylation status and congenital septal defects. The DNA methylation of seven CpG sites in the TBX20 gene promoter was analyzed through pyrosequencing as a quantitative method in 48 patients with congenital septal defects and 104 individuals with patent ductus arteriosus (PDA). The average methylation was higher in patients than in PDA (p < 0.001). High methylation levels were associated with a higher risk of congenital septal defects (OR = 4.59, 95% CI = 1.57-13.44, p = 0.005). The ROC curve analysis indicated that methylation of the TBX20 gene could be considered a risk marker for congenital septal defects (AUC = 0.682; 95% CI = 0.58-0.77; p < 0.001). The analysis of environmental risk factors in patients with septal defects and PDA showed an association between the consumption of vitamins (OR = 0.10; 95% CI = 0.01-0.98; p = 0.048) and maternal infections (OR = 3.10; 95% CI = 1.26-7.60; p = 0.013). These results suggest that differences in DNA methylation of the TBX20 gene can be associated with septal defects.

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

The TBX5 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 TBX5 gene promoter and congenital septal defects. DNA methylation levels of six CpG sites in the TBX5 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 (p < 0.004). In five CpG sites, we also found higher methylation levels in patients than in the controls (p < 0.05). High methylation levels were associated with congenital septal defects (OR = 3.91; 95% CI = 1.02-14.8; p = 0.045). The analysis of Receiver Operating Characteristic (ROC) showed that the methylation levels of the TBX5 gene could be used as a risk marker for congenital septal defects (AUC = 0.68, 95% CI = 0.56-0.80; p = 0.004). Finally, an analysis of environmental factors indicated that maternal infections increased the risk (OR = 2.90; 95% CI = 1.01-8.33; p = 0.048) of congenital septal defects. Our data suggest that a high DNA methylation of the TBX5 gene could be associated with congenital septal defects.

Association between congenital heart disease and NKX2.5 gene polymorphisms: systematic review and meta-analysis.

Aim: To analyze the association of NKX2.5 gene with congenital heart disease (CHD), and to determine if the variants rs703752, rs3729753 and rs2277923 increase the risk for developing CHD. Materials & methods: PubMed, EBSCO and Web of Science databases were screened to identify eligible studies. Through a comprehensive meta-analysis software, the association between NKX2.5 gene variants and susceptibility of CHD was calculated by pooled odd ratio (ORs) and 95% CI. Results: We observed that the allelic model of rs703752 and rs2277923 increased the risk in the overall population: OR = 1.24; 95% CI: 1.00-1.55; Z p-value = 0.049; OR = 1.18; 95% CI: 0.01-1.37; Z p-value = 0.036; respectively. Conclusion: Our results suggested that the rs703752 and rs2277923 polymorphisms of the NKX2.5 gene are associated with CHD.

The rs46522 Polymorphism of the Ubiquitin-Conjugating Enzyme E2Z Gene Is Associated with Abnormal Metabolic Parameters in Patients with Myocardial Infarction: The Genetics of Atherosclerosis Disease Mexican Study.

The participation of ubiquitin-conjugating enzyme E2Z (UBE2Z) in atherosclerosis has been reported. We aimed to evaluate the association of the rs46522 polymorphism of the UBE2Z gene with myocardial infarction (MI) and other clinical and metabolic components in the Mexican population. A total of 2128 individuals (1023 patients with MI and 1105 healthy controls) were included. rs46522 was genotyped using the 5' exonuclease TaqMan genotyping assay. A similar polymorphism distribution was observed between patients and healthy controls. The association between rs46522 polymorphism and cardiometabolic parameters was evaluated separately in the two groups. In the control group, rs46522 polymorphism was associated with increased risk of developing low-density lipoprotein cholesterol ≥130 mg/dL (odds ratio [OR] = 1.249, padditive = 0.018; OR = 1.479, precessive = 0.015; OR = 1.589, pcodominant 2 = 0.013). On the other hand, in MI patients, it was observed that rs46522 polymorphism was associated with an increased risk of developing high levels of alanine transaminase (OR = 1.297, pheterozygote = 0.043) and aspartate transaminase (OR = 1.453, pdominant = 0.009; OR = 1.592, pheterozygote = 0.001; OR = 1.632, pcodominant 1 = 0.001). Our results suggest that the UBE2Z gene rs46522 polymorphism is associated with abnormal metabolic parameters in Mexican patients with MI.

Interleukin 6 (rs1800795) gene polymorphism is associated with cardiovascular diseases: a meta-analysis of 74 studies with 86,229 subjects.

Cardiovascular diseases (CVD) are group of complex and multifactorial pathologies, in which interleukin-6 (IL-6) gene polymorphisms have been associated with several components of the CVD. Thus, in this study, we thoroughly reviewed and meta-analyzed evidence on the association between the IL-6 (rs1800795) gene polymorphism and CVD. We systematically searched in the PubMed, Web of Sciences, and Scopus databases. The analyses were performed using five study groups based on (1) a combined pool of the overall populations, (2) the country of birth, (3) the continent of birth, (4) the diagnosis and (5) both location (country or continent) and diagnosis. The analysis included the allelic, homozygote, heterozygote, dominant and recessive models. The meta-analysis showed that -174G>C (rs1800795) is a risk factor for CVD (allelic: OR=1.06, CI 95%=1.02-1.10. Z p value <0.0001; homozygous: OR=1.11, CI 95%=1.03-1.19, Z p value= 0.002; heterozygous: OR=1.08, CI 95%=1.03-1.21, Z p value= 0.003; dominant: OR= 1.12, CI 95%= 1.07-1.18, Z p value= 0.001) and that this risk increases in the Chinese population. Additionally, we found that carriers of the C allele of 174G>C (rs1800795) polymorphism have an increase in the risk of coronary artery disease under the hereditary models assessed in the study. Using robust data, we found that IL-6 (rs1800795) -174G>C gene polymorphism is associated with CVD risk.

A haplotype of the phosphodiesterase 4D (PDE4D) gene is associated with myocardial infarction and with cardiometabolic parameters: the GEA study.

The phosphodiesterase family is involved in a wide spectrum of diseases, including ischemic stroke. However, few studies have analyzed the relationship between phosphodiesterase 4D (PDE4D) and myocardial infarction (MI). Therefore, the aim of this research was to evaluate the association of the PDE4D gene polymorphisms with MI, and with cardiometabolic parameters in the Mexican population. Six polymorphisms (rs2910829, rs1423246, rs966221, rs4502776, rs13172481, and rs6869495) were genotyped in 1023 MI patients and 1105 healthy controls. A similar distribution of the six polymorphisms was observed in both studied groups. However, after evaluating the linkage disequilibrium, we detected a risk haplotype for MI (AGAGAA; OR = 1.148; P = 0.025). In addition, the polymorphisms were associated with the presence of some clinical and metabolic parameters (central obesity, hypertriglyceridemia, Aspartate transaminase >p75, Lipoprotein (a) >30 mg/dL, TAT >p75, fatty liver, and vitamin D <30 ng/dL) in healthy controls. The results suggest that in the Mexican population, a PDE4D haplotype is associated with increased risk of developing MI, and that PDE4D polymorphisms are independently associated with the presence of cardiometabolic parameters.