The genetic analysis of the G742A polymorphism targets a specific variant of the BHMT gene (Betaine-Homocysteine S-Methyltransferase), which encodes the BHMT enzyme, a key enzyme involved in the alternative remethylation pathway of homocysteine. This test detects a guanine (G) to adenine (A) substitution at nucleotide position 742, a genetic change that affects BHMT enzyme activity, methylation efficiency, and homocysteine metabolism. Since BHMT catalyzes the conversion of homocysteine to methionine using betaine as a methyl donor, BHMT gene variants can influence one-carbon (1C) metabolism, cellular methylation processes, and susceptibility to conditions associated with impaired methylation, including cardiovascular diseases, neurological disorders, and metabolic dysregulation.
The methylation cycle is a fundamental biochemical pathway that regulates DNA methylation, gene expression, lipid metabolism, and neurotransmitter synthesis. BHMT is vital in this cycle, providing an alternative route for homocysteine detoxification—particularly in the liver and kidneys—by reducing homocysteine accumulation and supporting the production of methionine. The BHMT G742A polymorphism (rs3733890) has been associated with changes in enzyme activity, with the A allele linked to increased BHMT function. Enhanced enzyme activity leads to more efficient betaine-dependent remethylation of homocysteine, resulting in reduced plasma homocysteine levels, which are considered protective against cardiovascular and neurological conditions.
The A allele has been associated with lower homocysteine concentrations, which may help prevent endothelial dysfunction, oxidative stress, and vascular injury, thereby potentially reducing the risk of atherosclerosis, coronary artery disease, and stroke. Elevated homocysteine has been linked to decreased bioavailability of nitric oxide (NO), diminished vasodilation, and increased vascular inflammation. Improved methylation efficiency also influences lipid metabolism, with studies suggesting that BHMT polymorphisms may be associated with alterations in cholesterol and triglyceride levels, further impacting cardiovascular risk.
The G742A polymorphism has also been linked to nervous system health, as methylation plays a crucial role in neurotransmitter production, myelin maintenance, and cognitive function. Elevated homocysteine has been linked to neurodegenerative diseases such as Alzheimer's and Parkinson's, where disrupted methylation processes may contribute to neuroinflammation, synaptic dysfunction, and neuronal damage. Additionally, the G742A variant has been associated with psychiatric conditions such as depression and schizophrenia, in which homocysteine metabolism and methylation may impact neurotransmitter regulation and brain function.
Beyond its cardiovascular and neurological effects, the G742A polymorphism has been investigated in the context of metabolic disorders, as methylation influences insulin signaling, liver function, and lipid metabolism. Reduced BHMT activity—where present—has been associated with a higher risk of metabolic syndrome, non-alcoholic fatty liver disease (NAFLD), and type 2 diabetes, which are characterized by insulin resistance, inflammation, and dyslipidemia. Disruptions in betaine-dependent methylation have also been linked to DNA instability and epigenetic dysregulation, with potential implications for cancer risk, especially in the liver and colon, where betaine metabolism is crucial for cellular integrity.
Genetic screening for the BHMT G742A polymorphism provides valuable insights into an individual's predisposition to disturbances in homocysteine metabolism, methylation capacity, and associated disease risks. Identifying this polymorphism enables assessment of one-carbon cycle function, cardiovascular and neurological health, and metabolic regulation, contributing to a deeper understanding of the genetic impact on physiological processes that depend on methylation.
The genetic testing of the BHMT gene, G742A polymorphism, is also included in the tests:
- Methylation Genetic Testing, MethylGenomiX® Basic Panel
- Methylation Genetic Testing, MethylGenomiX® Comprehensive Panel
Last updated: 22/07/2025
