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Background/Objectives: The objective of the study was to assess the role of variations in serum folate, vitamin B12, homocysteine and the presence of genetic polymorphisms as risk factors for congenital heart disease (CHD) in children. Subjects/Methods: A total of 32 children with CHD, and their mothers and 32 normal children and their mothers formed the study and control groups, respectively. Serum folate, vitamin B12 and homocysteine as well as genetic polymorphisms MTHFR C677[right arrow]T, MTHFR A1298[right arrow]C, MTR A2756[right arrow]G and MTRR A66[right arrow]G were assessed. Results: Low serum folate and genetic polymorphisms MTHFR C677[right arrow]T and MTRR A66[right arrow]G among children and their mothers and high homocysteine among mothers were noted as risk factors for CHD (P Conclusions: Low serum folate, high homocysteine and presence of selected genetic polymorphisms among children and their mothers were noted as risk factors for CHD. Nutrient-gene interaction being a modifiable risk factor, the study recommends the use of peri-conceptional folate supplementation with vitamin B12 sufficiency for primary prevention of CHD., Author(s): K E Elizabeth [sup.1] , S L Praveen [sup.1] , N R Preethi [sup.2] , V T Jissa [sup.2] , M R Pillai [sup.2] Author Affiliations: (1) Department of [...]

Genetic factors undoubtedly affect the development of congenital heart disease (CHD) but still remain ill defined. We sought to identify genetic risk factors associated with CHD and to accomplish a functional analysis of SNP-carrying genes. We performed a genome-wide association study (GWAS) of 4034 White patients with CHD and 8486 healthy controls. One SNP on chromosome 5q22.2 reached genome-wide significance across all CHD phenotypes and was also indicative for septal defects. One region on chromosome 20p12.1 pointing to the MACROD2 locus identified 4 highly significant SNPs in patients with transposition of the great arteries (TGA). Three highly significant risk variants on chromosome 17q21.32 within the GOSR2 locus were detected in patients with anomalies of thoracic arteries and veins (ATAV). Genetic variants associated with ATAV are suggested to influence the expression of WNT3, and the variant rs870142 related to septal defects is proposed to influence the expression of MSX1. We analyzed the expression of all 4 genes during cardiac differentiation of human and murine induced pluripotent stem cells in vitro and by single-cell RNA-Seq analyses of developing murine and human hearts. Our data show that MACROD2, GOSR2, WNT3, and MSX1 play an essential functional role in heart development at the embryonic and newborn stages., Introduction Congenital heart disease (CHD) accounts for approximately 28% of all congenital anomalies worldwide (1), with a CHD frequency of 9.1 per 1000 live births (2). Currently, CHD represents a [...]

Maternal age is a risk factor for congenital heart disease even in the absence of any chromosomal abnormality in the newborn (1-7). Whether the basis of this risk resides with the mother or oocyte is unknown. The impact of maternal age on congenital heart disease can be modelled in mouse pups that harbour a mutation of the cardiac transcription factor gene Nkx2-5 (ref. 8). Here, reciprocal ovarian transplants between young and old mothers establish a maternal basis for the age-associated risk in mice. A high-fatdiet does not accelerate the effect of maternal ageing, so hyperglycaemia and obesity do not simply explain the mechanism. The age-associated risk varies with the mother's strain background, making it a quantitative genetic trait. Most remarkably, voluntary exercise, whether begun by mothers at a young age or later in life, can mitigate the risk when they are older. Thus, even when the offspring carry a causal mutation, an intervention aimed at the mother can meaningfully reduce their risk of congenital heart disease., Congenital heart disease remains a leading cause of childhood morbidity and mortality despite dramatic clinical advances. Discoveries regarding the pathogenic mechanisms have likewise abounded, but translating knowledge about the causes [...]