Folate, vitamin B12, homocysteine and polymorphisms in folate metabolizing genes in children with congenital heart disease and their mothers

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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→T, MTHFR A1298→C, MTR A2756→G and MTRR A66→G were assessed.RESULTS:Low serum folate and genetic polymorphisms MTHFR C677→T and MTRR A66→G among children and their mothers and high homocysteine among mothers were noted as risk factors for CHD (P < 0.05). Vitamin B12 levels were normal and showed no association. Presence of MTHFR C677→T and MTRR A66→G, both concurrently among children as well as mothers and simultaneously among mother-child pairs, showed several fold increase in the risk for CHD. On multivariate analysis, the risk factors noted for CHD were presence of MTHFR C677→T among children and their mothers and MTRR A66→G among mothers. Analyses for nutrient-gene interaction revealed significant associations between low serum folate and high serum homocysteine levels, and the presence of selected genetic polymorphisms.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.

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