Relationships between Maternal Folic Acid Supplementation and GATA4 Gene Polymorphisms in Patients with Non-Chromosomal Congenital Heart Disease: A Hospital-Based Case-Control Study in China

This study aimed to investigate the relationships between maternal FA supplementation and nine single-nucleotide variants of the GATA4 gene in non-chromosomal CHD and further explore the gene-environment interactions associated with CHD. A total of 585 CHD patients and 600 controls were recruited in the case-control study. Maternal FA (FA-containing multivitamin) supplementation information and nine polymorphisms of the GATA4 gene were collected in this study. Adjusted ORs (aOR) and their 95% confidence intervals (CIs) were calculated using proper statistical methods to analyze the relationships between the two main exposures of interest with respect to CHD. After adjusting the suspicious confounding factors, a significantly increased risk for CHD in offspring was found with non-FA supplementation before/during the pregnancy to CHD in offspring (aOR = 1.58, 95% CI: 1.01-2.48). We suggested taking FA supplementation before/during the pregnancy to prevent CHD in offspring, especially in the preconception period (aOR = 0.53, 95% CI: 0.32-0.90). The genetic results showed that the polymorphisms of rs4841588, rs12458, and rs904018 under specific genotypes and genetic models were significantly related to CHD. The gene-environment interaction between rs10108052 and FA supplementation before/during pregnancy could increase the risk of CHD (aOR = 5.38, 95% CI: 1.67-17.09, Pinteraction = 0.004). Relationships between maternal FA supplementation and specific polymorphisms of the GATA4 gene, as well as the gene-environment interaction, were significantly associated with CHD in offspring.