The BHMT G742A genetic test analyzes a specific variation in the BHMT gene, which encodes betaine-homocysteine S-methyltransferase (BHMT), an essential enzyme involved in the alternative pathway of homocysteine remethylation. This test detects a guanine (G) to adenine (A) substitution at nucleotide position 742, a genetic variation that influences BHMT enzyme activity, methylation efficiency, and homocysteine metabolism. Since BHMT catalyzes the conversion of homocysteine to methionine using betaine as a methyl donor, variations in BHMT affect one-carbon metabolism, cellular methylation processes, and susceptibility to conditions related to impaired methylation, including cardiovascular diseases, neurological disorders, and metabolic imbalances.
The methylation cycle is a core biochemical pathway that controls DNA methylation, gene expression, lipid metabolism, and neurotransmitter production. BHMT is crucial in this cycle by offering an alternative route for clearing homocysteine, especially in the liver and kidneys, where it helps reduce homocysteine buildup and supports methionine production. The BHMT G742A polymorphism has been linked to changes in enzyme activity, with research suggesting that the A allele may cause decreased BHMT function. Less efficient enzyme activity leads to reduced betaine-dependent homocysteine remethylation, resulting in elevated homocysteine levels, which are recognized as a significant risk factor for cardiovascular and neurological diseases.
The presence of the A allele has been associated with increased homocysteine levels, which contribute to endothelial dysfunction, oxidative stress, and arterial damage, promoting the development of atherosclerosis, coronary artery disease, and stroke. Elevated homocysteine levels disrupt nitric oxide (NO) bioavailability, thereby reducing vasodilation and increasing vascular inflammation. Impaired methylation efficiency also affects lipid metabolism, with reports of associations between BHMT polymorphisms and altered cholesterol and triglyceride levels, which further impact cardiovascular risk.
The impact of this polymorphism extends to neurological health, as methylation is crucial for the production of neurotransmitters, the maintenance of myelin, and cognitive function. Elevated homocysteine has been linked to neurodegenerative diseases, including Alzheimer’s and Parkinson’s diseases, where disrupted methylation processes lead to neuroinflammation, synaptic issues, and neuronal damage. The BHMT G742A polymorphism has also been connected to psychiatric conditions, such as depression and schizophrenia, where changes in homocysteine metabolism and methylation affect neurotransmitter regulation and brain function.
Beyond cardiovascular and neurological effects, the BHMT G742A polymorphism has been examined in relation to metabolic disorders, as methylation influences insulin signaling, liver function, and fat metabolism. Reduced BHMT activity has been associated with a higher risk of metabolic syndrome, non-alcoholic fatty liver disease (NAFLD), and type 2 diabetes, conditions marked by insulin resistance, inflammation, and abnormal lipid profiles. Impaired betaine-dependent methylation also impacts DNA stability and epigenetic regulation, with possible implications for cancer risk, especially in the liver and colon, where betaine metabolism is crucial for preserving cellular integrity.
Genetic testing for the BHMT G742A polymorphism provides insight into an individual’s genetic predisposition to altered homocysteine metabolism, impaired methylation efficiency, and associated disease risks. Identifying this variant enables an assessment of one-carbon cycle function, cardiovascular and neurological health, and metabolic regulation, thereby fostering a deeper understanding of the genetic influences on methylation-dependent physiological processes and disease susceptibility.
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: 29/06/2025
