The MAT1A D18777A polymorphism genetic test analyzes a specific variation in the MAT1A gene, which encodes methionine adenosyltransferase 1A (MAT1A), an essential enzyme responsible for the synthesis of S-adenosylmethionine (SAMe), the primary methyl donor in cellular methylation reactions. This test detects an aspartic acid (D) to alanine (A) substitution at nucleotide position 18777, a genetic variation that influences MAT1A enzyme activity, SAMe production, and methylation efficiency. As methylation plays a crucial role in gene regulation, neurotransmitter synthesis, lipid metabolism, and homocysteine clearance, variations in MAT1A affect numerous biological processes and contribute to the risk of liver diseases, neurological disorders, and metabolic imbalances.
The methionine cycle is a fundamental metabolic pathway that maintains the supply of methyl groups required for DNA methylation, protein function, and lipid metabolism. MAT1A catalyzes the conversion of methionine to SAMe, which donates methyl groups to various acceptors, including DNA, RNA, proteins, and neurotransmitters. The MAT1A D18777A polymorphism has been associated with alterations in enzymatic activity, with studies suggesting that the A allele may lead to reduced MAT1A function and lower SAMe production. Impaired SAMe synthesis results in inefficient methylation reactions, affecting epigenetic regulation, phospholipid metabolism, and homocysteine homeostasis.
The A allele has been linked to an increased risk of liver dysfunction, as MAT1A is highly expressed in hepatocytes and plays a critical role in maintaining liver methylation balance. Reduced SAMe levels contribute to hepatic oxidative stress, impaired lipid metabolism, and increased susceptibility to non-alcoholic fatty liver disease (NAFLD), liver fibrosis, and cirrhosis. Studies have demonstrated that individuals carrying the A allele may exhibit altered liver function markers, with associations reported between MAT1A polymorphisms and hepatocellular carcinoma risk due to disrupted methylation-dependent gene expression.
The impact of this polymorphism extends to neurological health, as SAMe is essential for neurotransmitter synthesis, myelin maintenance, and cognitive function. Impaired methylation due to reduced MAT1A activity has been associated with neurodegenerative disorders, including Alzheimer’s disease and Parkinson’s disease, where disrupted SAMe metabolism contributes to synaptic dysfunction, neuronal damage, and oxidative stress. The MAT1A D18777A polymorphism has also been implicated in psychiatric conditions such as depression and schizophrenia, as SAMe plays a role in the regulation of serotonin, dopamine, and norepinephrine, neurotransmitters involved in mood stability and cognitive processes.
Beyond liver and neurological health, the MAT1A D18777A polymorphism has been studied in cardiovascular and metabolic diseases, as methylation is crucial for lipid metabolism, homocysteine clearance, and vascular function. Reduced SAMe production has been linked to elevated homocysteine levels, a known risk factor for atherosclerosis, coronary artery disease, and stroke. Additionally, impaired phospholipid methylation may contribute to dyslipidemia, insulin resistance, and metabolic syndrome, further increasing cardiovascular risk. The role of this polymorphism in cancer susceptibility has also been explored, as disrupted DNA methylation patterns due to altered SAMe availability may influence tumorigenesis in various tissues.
Genetic testing for the MAT1A D18777A polymorphism provides insight into an individual’s genetic predisposition to altered methylation capacity, liver function, neurological health, and cardiovascular risk. Identifying this variant allows for assessing SAMe production efficiency, one-carbon metabolism function, and susceptibility to methylation-related disorders, contributing to a deeper understanding of genetic influences on cellular methylation and disease development.
The genetic testing of D18777A Polymorphism of the MAT1A gene is also included in the tests:
