Related Experiment Video
Updated: Aug 13, 2025
03:19
Author Spotlight: Studying the Impact of Maternal Dietary Deficiencies on Long-Term Offspring Health Outcomes
Published on: June 28, 2024
483
Gene-Folic Acid Interactions and Risk of Conotruncal Heart Defects: Results from the National Birth Defects
Daniel M Webber1, Ming Li2, Stewart L MacLeod3
1Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA.
Genes
|January 21, 2023
Summary
Maternal folate intake and genetic variations in folate-related genes influence conotruncal heart defect (CTD) risk. Folic acid supplementation may reduce CTD risk in genetically susceptible individuals.
Area of Science:
- Genetics
- Cardiology
- Public Health
Background:
- Conotruncal heart defects (CTDs) are severe congenital heart malformations with significant health impacts.
- Maternal folate intake is linked to reduced heart defect risk, but gene-folate interactions remain unclear.
Purpose of the Study:
- To investigate the interactive effects of folate-related gene variants and maternal folate intake on CTD risk.
- To identify specific genetic variants associated with CTD susceptibility.
Main Methods:
- Targeted sequencing of folate-related genes in 436 CTD case families from the National Birth Defects Prevention Study.
- Analysis of common and rare variants, including de novo mutations, in folate, homocysteine, and transsulfuration pathways.
Main Results:
- Identified risk alleles in maternal MTHFS and NOS2, and fetal MTHFS and TCN2 associated with increased CTD risk without folic acid supplementation.
- Found a significant association between rare MGST1 variants and CTD risk.
- Periconceptional folic acid supplementation was linked to a decreased CTD risk in individuals with susceptible genotypes.
Conclusions:
- Genetic variations in folate metabolism pathways interact with folic acid supplementation to modify CTD risk.
- Targeted genetic screening and periconceptional folic acid supplementation could be key strategies for CTD prevention.
Related Concept Videos
01:07Teratogenicity
2.6K
The ability of a drug to produce structural deformations and functional abnormalities in the developing embryo or the fetus is called teratogenicity, and the drug producing this effect is known as a teratogen. Teratogenic effects include stillbirth, miscarriage, intrauterine growth restriction, and neurocognitive delay. A teratogen may affect the embryo at different stages of development, which is important in determining the type and extent of the damage. During blastocyst formation, the early...
2.6K
01:18Anticoagulant Drugs: Vitamin K Antagonists and Direct Oral Anticoagulants
1.3K
Oral anticoagulants are vital tools in preventing and treating blood clotting disorders. This diverse class of medications can be categorized as vitamin K antagonists, exemplified by warfarin, and direct thrombin inhibitors (DTIs), such as dabigatran, as well as factor Xa inhibitors, including rivaroxaban.
Warfarin, a prominent vitamin K antagonist family member, exerts its effect by inhibiting the enzyme VKORC1 (vitamin K epoxide reductase complex 1). By hindering this enzyme, warfarin...
Warfarin, a prominent vitamin K antagonist family member, exerts its effect by inhibiting the enzyme VKORC1 (vitamin K epoxide reductase complex 1). By hindering this enzyme, warfarin...
1.3K
01:23Factors Affecting Protein-Drug Binding: Drug Interactions
240
Drug interactions are a critical aspect of pharmacology and can occur when two or more drugs compete for the same binding site. This competition can result in one drug displacing another, altering the effect of the displaced drug. Drug interactions are complex processes that rely heavily on how much of the displacer drug is present and how strongly it can bind to the same sites as the displaced drug.
Displacement interactions can have varying outcomes, ranging from toxicity to virtually...
Displacement interactions can have varying outcomes, ranging from toxicity to virtually...
240
01:27Combined Effects of Drugs: Synergism
4.4K
Synergism is a useful mechanism where combining two or more drugs is more effective than each constituent used alone. Such combinations are also called supra-additive interactions. The drugs collectively enhance the final therapeutic effect by acting on different targets. Another advantage is that the low dose of each constituent drug is sufficient to achieve the desired effect. This helps reduce the duration of therapy and lower the adverse effects of these drugs.
Such synergistic combinations...
Such synergistic combinations...
4.4K
01:20Gene-Environment Interactions
395
Gene expression is a dynamic process that is significantly influenced by environmental factors. This interaction underlies the complex nature of biological development and the phenotypic differences observed among individuals, even among those with identical genetic makeups. Factors such as radiation, temperature, behavior, nutrition, and stress play pivotal roles in determining how genes are expressed. The concept of the reaction range is central to understanding this interaction. It posits...
395
01:20Inborn Errors of Metabolism
221
Phenylketonuria (PKU) is a protein metabolism disorder characterized by high blood levels of the amino acid phenylalanine. This results from a mutation in the gene responsible for phenylalanine hydroxylase, an enzyme that converts phenylalanine into tyrosine. When this enzyme is deficient, phenylalanine builds up in the blood, leading to symptoms such as vomiting, rashes, seizures, growth deficiency, and severe mental retardation. An early diagnosis and a diet restricting phenylalanine intake...
221