Genes and the Heart: The Hidden Link of MTHFD1-G1958A

11 février 2025

#Cardiology #CongenitalHeartDisease #GeneEnvironmentInteraction #MTHFD1 Congenital heart diseases (CHD) are among the most common birth defects, affecting approximately 1 to 1.2% of newborns. Their origin is multifactorial, resulting from a complex interaction between genetic predispositions and environmental factors. Among the genes involved, MTHFD1 plays a central role in folate metabolism and t

#Cardiology #CongenitalHeartDisease #GeneEnvironmentInteraction #MTHFD1

Congenital heart diseases (CHD) are among the most common birth defects, affecting approximately 1 to 1.2% of newborns. Their origin is multifactorial, resulting from a complex interaction between genetic predispositions and environmental factors. Among the genes involved, MTHFD1 plays a central role in folate metabolism and the regulation of homocysteine levels, a compound essential for embryonic heart formation. Disruptions in this metabolic pathway can impair fetal heart development, increasing the risk of congenital heart malformations. The MTHFD1-G1958A polymorphism (rs2236225) has been proposed as a potential susceptibility factor for CHD, but study results remain contradictory.

This study explores the association between this polymorphism and CHD risk to improve the understanding of the genetic mechanisms underlying these anomalies.

MTHFD1-G1958A: A Hidden Risk Factor for Congenital Heart Disease?

Nine studies including 1,917 children with CHD and 1,863 healthy controls, as well as 1,717 mothers of affected children and 1,666 control mothers, were selected. The association between the MTHFD1-G1958A polymorphism and CHD risk was evaluated using multiple genetic models, with the calculation of odds ratios (OR) and 95% confidence intervals (CI) to measure the strength of the association.

The primary analysis did not reveal a significant association between the MTHFD1-G1958A polymorphism and the overall CHD risk in children. However, a significant association was found in the Tetralogy of Fallot (TOF) subtype, suggesting a potential role of the polymorphism in this heart defect. In mothers, the analysis showed that the MTHFD1-G1958A polymorphism was associated with an increased risk of CHD in the tested models.

Additionally, racial differences were observed: the MTHFD1-G1958A polymorphism was associated with a higher CHD risk in Caucasian populations but not in Asian populations.

Read next: Fragility and cognitive profile of adult and elderly subjects with congenital heart disease

CHD and Genetics: Decoding the Heart’s Blueprint

Congenital heart diseases are the most common birth defects, with a prevalence of 1 to 1.2%. Their etiology is based on a complex interaction between genetic and environmental factors, making prevention and early detection challenging.

Despite advances in genetics, identifying specific risk factors remains a challenge. While the MTHFD1-G1958A polymorphism has been proposed as a genetic marker influencing CHD development, previous studies have yielded contradictory results. This meta-analysis explores the link between this polymorphism and CHD risk, considering specific subtypes and racial variations.
The findings confirm a significant correlation between the MTHFD1-G1958A polymorphism and CHD risk in certain subgroups, particularly Tetralogy of Fallot and certain Caucasian populations. These data reinforce the idea that genetic predisposition plays a key role in congenital heart disease susceptibility, opening new perspectives for screening.

Further studies on larger and more diverse cohorts will be needed to validate these observations and understand the underlying biological mechanisms. Additionally, the impact of environmental factors on the expression of this polymorphism remains to be explored. Ultimately, identifying reliable genetic markers could improve prevention strategies and early CHD screening, enabling more personalized and targeted care for at-risk patients.

Read next: L-arginine: a promising advance for reducing inflammatory and cardiac markers after coronary artery bypass surgery

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Scientific reference

Yi, K., He, et al. (2025). Association of MTHFD1 G1958A (rs2236225) gene polymorphism with the risk of congenital heart disease: a systematic review and meta-analysis. BMC medical genomics, 18(1), 20.

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