Congenital heart disease (CHD) describes a huge set of structural and functional abnormalities that arises during cardio embryogenesis. Low levels of maternal vitamin B12 can disturb the homeostasis of the fetal folate metabolism pathway. The gene CUBN encodes for the intrinsic factor– cobalamin receptor (cubilin), which acts as a receptor for intrinsic factor to many compounds such as vitamin B12.Main aim of our study was to analyze association of CUBN G253A (rs1801222) variant with maternal serum folate, vitamin B12 and homocysteine (Hcy) levels and thereby its link with congenital heart defects. 110 pregnant women with vitamin B12 deficiency and carrying fetuses with CHD and equal number of age matched healthy women were selected as cases and control subjects respectively. Maternal serum folate, vitamin B12 and homocysteine levels as well as genetic polymorphism CUBN G253 → A were assessed. In the present study, it was observed that cases with GA genotype, A allele under the dominant (p=<0.001) and allelic models (p<0.001) respectively and cases with AA genotype under the co-dominant (p<0.01) and recessive models (p<0.001) demonstrated an increased risk of an offspring with CHD. Furthermore, while cases with GA and AA genotypes of CUBN G253A variant showed significantly elevated Homocysteine, it was observed that all the CHD case mothers were vitamin B12 deficient irrespective of the CUBN genotype.

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