Meta-Analyses of Epigenetic Factors in the Prevention of Congenital Heart Defects: MTHFR C677T Human Gene Variations across Generations from Parents to Children

The purpose of this study is to disseminate current evidence on Methylenetetrahydrofolate reductase (MTHFR) gene mutations in children and their parents, and related epigenetic factors in the prevention of the children’s congenital heart defects (CHD), through meta-analyses.

MTHFR gene plays an important role in the methylation pathway for health and wellbeing across generations in the development of CHD. The association between the polymorphisms of MTHFR and CHD is contentious, thus we conducted meta-analyses on MTHFR gene mutations and related epigenetic factors across generations in the development of CHD. Quality scores for the studies, and inter-rater evaluation on data coding was completed to ensure data accuracy for pooled meta-analyses.

Preliminary results included 4039 cases and 6849 controls from 31 studies for children, 817 cases and 836 controls from 16 studies for mothers, as well as 246 cases and 300 controls from 6 studies for fathers, of children with CHD. Based on children’s and their parents’ genotypes, MTHFR 677 TT homozygous mutation type was associated with increased risk (p < 0.05), whereas 677 CC wild genotype was protective for children from CHD (p < 0.05). Maternal folate supplementation during preconception and gestation was associated with a decreased risk of CHD (RR = 0.60, p < 0.01, 5 studies, 761 cases and 1428 controls). On the other hand, no supplementation of folate during preconception and gestation for mothers was associated with an increased risk of CHD (RR=1.26, p < 0.05). Maternal smoking was potentially associated with the development of CHD (3 studies, 799 cases and 1113 controls, RR =1.156, p = 0.053).

Future studies are needed to examine epigenetic factors associated with MTHFR gene variations in the prevention of CHD across generations.