Related Experiment Video
Updated: Jun 6, 2026
Fetal Mouse Cardiovascular Imaging Using a High-frequency Ultrasound (30/45MHZ) System
Published on: May 5, 2018
MTHFR C677T and A1298C polymorphisms as a risk factor for congenital heart defects in Down syndrome
Ivana Babić Božović1, Jadranka Vraneković, Nada Starčević Cizmarević
1Department of Biology and Medical Genetics, School of Medicine, University of Rijeka, Rijeka, Croatia.
Insights
This study found no link between MTHFR gene variants and congenital heart defects (CHD) in Down syndrome (DS) individuals in Croatia. Maternal MTHFR polymorphisms were not identified as a risk factor for CHD in DS children.
Area of Science:
- Genetics and Molecular Biology
- Pediatrics
- Public Health
Background:
- Congenital heart defects (CHD) are common in Down syndrome (DS), but not universal.
- Methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms (C677T and A1298C) have been investigated as potential risk factors for CHD in DS.
- Understanding genetic contributions is crucial for DS and CHD research.
Purpose of the Study:
- To determine the frequency of MTHFR C677T and A1298C polymorphisms in Croatian DS individuals.
- To investigate the association between maternal MTHFR polymorphisms and CHD in DS children.
- To analyze the transmission patterns of MTHFR variant alleles in families with CHD-affected DS.
Main Methods:
- A case-control study involving 112 DS subjects and 221 controls from the Croatian population.
- Analysis of MTHFR C677T and A1298C genotypes in DS individuals and their mothers.
- Parent-offspring triad analysis for 34 families to examine allele transmission.
Main Results:
- No statistically significant differences in MTHFR C677T and A1298C allele or genotype frequencies were observed between DS subjects and controls.
- Maternal MTHFR polymorphisms were not identified as a significant risk factor for CHD in DS children.
- Allele transmission analysis showed no deviation from random segregation for the studied MTHFR polymorphisms.
Conclusions:
- The MTHFR C677T and A1298C polymorphisms do not appear to be major genetic risk factors for CHD in the Croatian DS population.
- Further research should consider both maternal and fetal MTHFR genotypes, alongside maternal nutrition and lifestyle, to fully understand CHD development in DS.
- Investigating factors beyond live-born individuals is essential due to potential pregnancy losses in trisomy 21.
Background:
Congenital heart defects (CHD) are present in most, but not all, cases of Down syndrome (DS). The presence of methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C polymorphisms has been reported as a risk factor for CHD in DS. The aims of the present study were to assess (i) the frequency of MTHFR C677T and A1298C polymorphisms in DS individuals in the Croatian population; (ii) the relationship between the two maternal MTHFR polymorphisms and CHD-affected DS children; and (iii) the transmission frequencies of the variant alleles of the two MTHFR polymorphisms in CHD-affected DS.
Methods:
The study population included 112 DS subjects and 221 controls. CHD were present in 48% of the DS subjects (54/112). The mothers of 107 DS individuals were available for the study; none was a periconceptional folic acid user. Allele transmission was analyzed in 34 complete parent-offspring triads.
Results:
The frequencies of the allele, individual, and combined genotypes of MTHFR C677T and A1298C in DS subjects were not statistically different compared to the normal healthy Croatian controls. The maternal MTHFR polymorphisms were not found to be a risk factor for DS-related CHD. The allele transmission of the two MTHFR polymorphisms showed no deviations from random segregation.
Conclusions:
Because the fetus is lost in a great proportion of trisomy 21 pregnancies, both maternal and fetal, not only live-born MTHFR C677T and A1298C, as well as maternal nutrition and lifestyle during pregnancy, should be analyzed to asses the impact on CHD in DS.
More Related Videos
Related Concept Videos
01:29Pharmacogenetic Phenotypes: Alterations in Pharmacokinetics, Drug Targets and Biologic Milieu
01:31Translation
Translation is the process of synthesizing proteins from the genetic information carried by messenger RNA (mRNA). Following transcription, it constitutes the final step in the expression of genes. This process is carried out by ribosomes, complexes of protein and specialized RNA molecules. Ribosomes, transfer RNA (tRNA), and other proteins produce a chain of amino acids—the polypeptide—as the end product of translation.
Translation Produces the Building Blocks of Life
01:31Translation
Translation is the process of synthesizing proteins from the genetic information carried by messenger RNA (mRNA). Following transcription, it constitutes the final step in the expression of genes. This process is carried out by ribosomes, complexes of protein and specialized RNA molecules. Ribosomes, transfer RNA (tRNA), and other proteins produce a chain of amino acids—the polypeptide—as the end product of translation.
Translation Produces the Building Blocks of Life
01:11Pharmacogenetics of Drug Targets: β₂-Adrenergic Receptors, Apo E, Thymidylate Synthase
02:57Meiosis vs. Mitosis
Before the start of mitosis and meiosis I, the cell synthesizes DNA, resulting in two homologous copies of each chromosome. DNA synthesis is...
01:49Meiosis I