Maternal Folic Acid Intake and Methylation Status of Genes Associated with Ventricular Septal Defects in Children: Case-Control Study.

Sandra M González-Peña,Geovana Calvo-Anguiano,Donato Saldivar-Rodríguez,Laura E Martínez-De-Villarreal,Patricia R Ancer-Rodríguez,María D Hernández-Almaguer,José J Lugo-Trampe,Luis D Campos-Acevedo,Ligia S Guerrero-Orjuela,Melissa Calzada-Dávila

doi:10.3390/nu13062071

Abstract

Background: DNA methylation is the best epigenetic mechanism for explaining the interactions between nutrients and genes involved in intrauterine growth and development programming. A possible contributor of methylation abnormalities to congenital heart disease is the folate methylation regulatory pathway; however, the mechanisms and methylation patterns of VSD-associated genes are not fully understood. Objective: To determine if maternal dietary intake of folic acid (FA) is related to the methylation status (MS) of VSD-associated genes (AXIN1, MTHFR, TBX1, and TBX20). Methods: Prospective case–control study; 48 mothers and their children were evaluated. The mothers’ dietary variables were collected through a food frequency questionnaire focusing on FA and the consumption of supplements with FA. The MS of promoters of genes was determined in the children. Results: The intake of FA supplements was significantly higher in the control mothers. In terms of maternal folic acid consumption, significant differences were found in the first trimester of pregnancy. Significant differences were observed in the MS of MTHFR and AXIN1 genes in VSD and control children. A correlation between maternal FA supplementation and MS of AXIN1 and TBX20 genes was found in control and VSD children, respectively. Conclusions: A lower MS of AXIN1 genes and a higher MS of TBX20 genes is associated with FA maternal supplementation.

Highlights

Folic acid (FA) deficiency is widespread and constitutes a significant global disease burden, which affects women during the reproductive period [1]
Given the limited literature available on gene–diet interaction, and on maternal folic acid intake and its relationship with the global methylation of genes associated with ventricular septal defects (VSD) (MTHFR, TBX1, TBX20, and AXIN1), this research aims to determine the relationship between maternal folic acid intake during pregnancy and the methylation status (MS) of genes associated with VSD
Regarding maternal intake of folic acid supplements, five women with a VSD child reported no consumption of folic acid supplements—they were excluded from the analysis of the association between maternal intake of folic acid supplements and the MS of genes associated with VSD

Summary

Introduction

Folic acid (FA) deficiency is widespread and constitutes a significant global disease burden, which affects women during the reproductive period [1]. Folate is an important substrate in carbon metabolism, by which carbon groups are provided for DNA methylation and DNA, RNA, proteins, and lipids synthesis [2]. The relevance of the relationship of folic acid intake with the prevention of congenital heart disease (CHD) has increased, which has led to a search for candidate genes involved in its metabolic pathway [4,5]. Objective: To determine if maternal dietary intake of folic acid (FA) is related to the methylation status (MS) of VSD-associated genes (AXIN1, MTHFR, TBX1, and TBX20). Significant differences were observed in the MS of MTHFR and AXIN1 genes in VSD and control children. A correlation between maternal FA supplementation and MS of AXIN1 and TBX20 genes was found in control and VSD children, respectively. Conclusions: A lower MS of AXIN1 genes and a higher MS of TBX20 genes is associated with FA maternal supplementation

Objectives

Methods

Conclusion