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

ABSTRACT: 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.

SUBMITTER: Garcia-Flores E

PROVIDER: S-EPMC9953838 | biostudies-literature | 2023 Feb

REPOSITORIES: biostudies-literature

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

García-Flores Esbeidy E Calderón-Colmenero Juan J Borgonio-Cuadra Verónica Marusa VM Sandoval Juan Pablo JP García-Montes José Antonio JA Cazarín-Santos Benny Giovanni BG Miranda-Duarte Antonio A Gamboa-Domínguez Armando A Rodríguez-Pérez José Manuel JM Pérez-Hernández Nonanzit N

Cells 20230211 4

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). Th ...[more]

PMID: 36831251

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Project description:Background Ventricular septal defects (VSD), when treated correctly in childhood, are considered to have great prognoses, and the majority of patients are discharged from follow-up when entering their teens. Young adults were previously found to have poorer functional capacity than healthy peers, but the question remains whether functional capacity degenerates further with age. Methods and Results A group of 30 patients with surgically closed VSDs (51±8 years) with 30 matched, healthy control participants (52±9 years) and a group of 30 patients with small unrepaired VSDs (55±12 years) and 30 matched control participants (55±10 years) underwent cardiopulmonary exercise testing using an incremental workload protocol and noninvasive gas measurement. Peak oxygen uptake was lower in participants with closed VSDs than matched controls (24±7 versus 34±9 mL/min per kg, P<0.01) and with unrepaired VSDs than matched controls (26±5 versus 32±8 mL/min per kg, P<0.01). Patients demonstrated lower oxygen uptake from exercise levels at 20% of maximal workload compared with respective control groups (P<0.01). Peak ventilation was lower in patients with surgically closed VSDs than control participants (1.0±0.3 versus 1.4±0.4 L/min per kg, P<0.01) but similar in patients with unrepaired VSDs and control participants (P=0.14). Exercise capacity was 29% lower in older patients with surgically closed VSDs than healthy peers, whereas younger patients with surgically closed VSDs previously demonstrated 18% lower capacity compared with peers. Older patients with unrepaired VSDs reached 21% lower exercise capacity, whereas younger patients with unrepaired VSDs previously demonstrated 17% lower oxygen uptake than healthy peers. Conclusions Patients with VSDs demonstrate poorer exercise capacity than healthy peers. The difference between patients and control participants increased with advancing age-and increased most in patients with operated VSDs-compared with previous findings in younger patients. Results warrant continuous follow-up for these simple defects.

Project description:BackgroundCongenital heart defects (CHD) are structural defects of the heart affecting approximately 1% of newborns. They exhibit low penetrance and non-Mendelian patterns of inheritance as varied and complex traits. While genetic factors are known to play an important role in the development of CHD, the specific genetics remain unknown for the majority of patients. To elucidate the underlying genetic risk, we performed a genome wide association study (GWAS) of CHDs in general and specific CHD subgroups using the FinnGen Release 10 (R10) (N > 393,000), followed by functional fine-mapping through eQTL and co-localization analyses using the GTEx database.ResultsWe discovered three genome-wide significant loci associated with general CHD. Two of them were located in chromosome 17: 17q21.32 (rs2316327, intronic: LRRC37A2, Odds ratio (OR) [95% Confidence Interval (CI)] = 1.17[1.12-1.23], p = 1.5 × 10-9) and 17q25.3 (rs1293973611, nearest: BAHCC1, OR[95%CI] = 4.48[2.80-7.17], p = 7.0 × 10-10), respectively, and in addition to general CHD, the rs1293973611 locus was associated with the septal defect subtype. The third locus was in band 1p21.2 (rs35046143, nearest: PALMD, OR[95%CI] = 1.15[1.09-1.21], p = 7.1 × 10-9), and it was associated with general CHD and left-sided lesions. In the subgroup analysis, two additional loci were associated with septal defects (rs75230966 and rs6824295), and one with left-sided lesions (rs1305393195). In the eQTL analysis the variants rs2316327 (general CHD), and rs75230966 (septal defects) both located in 17q21.32 (with a LD r2 of 0.41) were both predicted to significantly associate with the expression of WNT9B in the atrial appendage tissue category. This effect was further confirmed by co-localization analysis, which also implicated WNT3 expression in the atrial appendage. A meta-analysis of general CHD together with the UK Biobank (combined N = 881,678) provided a different genome-wide significant locus in LRRC37A2; rs16941382 (OR[95%CI] = 1.15[1.11-1.20], p = 1.5 × 10-9) which is in significant LD with rs2316327.ConclusionsOur results of general CHD and different CHD subcategories identified a complex risk locus on chromosome 17 near BAHCC1 and LRRC37A2, interacting with the genes WNT9B, WNT3 and MYL4, may constitute potential novel CHD risk associated loci, warranting future experimental tests to determine their role.

Project description:IntroductionCongenital heart defects (CHDs) are the most common congenital defects and accounts for nearly one-third of all major congenital anomalies. It is the leading causes of birth defect-associated morbidity, mortality, and medical expenditures. Of all CHD types, ventricular septal defect (VSD) and atrial septal defect (ASD) accounted 51% of cases with an increasing trend over time.ObjectiveThe aim of this review is to estimate the pooled prevalence of ventricular septal defect and congenital atrial septal defect among congenital heart diseases patients in East African context.MethodsUsing PRISMA guideline, we systematically reviewed and meta-analyzed studies that examined the prevalence of Ventricular septal defect and atrial septal defect in East Africa, from Medline (PubMed), Cochrane Library, HINARI, and Google Scholar. A weighted inverse variance random-effects model was used to estimate the pooled prevalence of ventricular septal defect and atrial septal defect.ResultsA total of 2323 studies were identified; 1301 from PubMed, 12 from Cochrane Library, 1010 from Google Scholar and 22 from other sources. The pooled prevalence of ventricular septal defect and atrial septal defect in East Africa was found to be 29.92% (95% CI; 26.12-33.72; I2 = 89.2%; p<0.001), and 10.36% (95% CI; 8.05-12.68; I2 = 89.5%; p<0.001) respectively.Conclusions and future implicationsBased on this review, the pooled prevalence of VSD and ASD is still high and alarming; this signifies that the emphasis given for congenital heart defect in East African countries is limited. Special attention and efforts should be applied for early detection to prevent serious complications and for a better prognosis of all forms of CHD. A screening program for CHD should be instituted during the perinatal period. Furthermore, early referral of suspected cases of congenital cardiac anomalies is mandatory for better management till the establishment of cardiac centers in different regions of the continent.

Dataset Information

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

Publications

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

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