The SHMT1 C1240T polymorphism genetic test analyzes a specific variation in the SHMT1 gene, which encodes serine hydroxymethyltransferase 1 (SHMT1), a crucial enzyme involved in one-carbon metabolism and folate-mediated nucleotide biosynthesis. This test detects a cytosine (C) to thymine (T) substitution at nucleotide position 1240, a genetic variation that influences SHMT1 enzyme activity, folate metabolism efficiency, and homocysteine regulation. As SHMT1 plays an essential role in converting serine to glycine while generating 5,10-methylenetetrahydrofolate (5,10-methylene-THF), variations in SHMT1 affect DNA synthesis, methylation processes, and susceptibility to conditions related to impaired folate metabolism, including neural tube defects, cardiovascular diseases, and cancer.
The one-carbon cycle is fundamental for maintaining cellular methylation and nucleotide synthesis, with SHMT1 functioning as a key enzyme in cytoplasmic folate metabolism. The SHMT1 C1240T polymorphism has been associated with alterations in enzyme activity, leading to variations in the availability of 5,10-methylene-THF, a critical cofactor for thymidylate synthase and methylenetetrahydrofolate reductase (MTHFR). Studies suggest that individuals carrying the T allele may exhibit increased SHMT1 enzyme activity, shifting folate metabolism toward nucleotide biosynthesis at the expense of methylation reactions. This metabolic shift results in lower levels of 5-methyltetrahydrofolate (5-methyl-THF), the primary methyl donor for homocysteine remethylation to methionine, leading to elevated homocysteine levels and increased cardiovascular risk.
The presence of the T allele has been linked to an increased susceptibility to neural tube defects (NTDs) due to impaired folate availability for DNA methylation and cellular proliferation during embryonic development. Reduced 5-methyl-THF levels hinder methylation-dependent gene regulation, affecting neural tube closure and fetal growth. Studies have suggested that maternal SHMT1 C1240T polymorphism and other folate-related gene variants, such as MTHFR C677T, may contribute to an elevated risk of congenital malformations.
The impact of this polymorphism extends to cancer susceptibility, as one-carbon metabolism plays a pivotal role in maintaining DNA integrity, repair, and epigenetic regulation. Variations in SHMT1 activity influence nucleotide pool balance and genomic stability, with the T allele being associated with an altered risk of colorectal, breast, and hematological malignancies. Impaired DNA methylation patterns resulting from reduced 5-methyl-THF availability have been implicated in tumorigenesis, as global hypomethylation promotes oncogene activation, while hypermethylation of tumor suppressor genes may drive cancer progression.
Beyond folate metabolism, the SHMT1 C1240T polymorphism has been investigated in relation to cardiovascular health, as elevated homocysteine levels contribute to endothelial dysfunction, oxidative stress, and thrombosis. Due to impaired homocysteine clearance, individuals with the T allele may exhibit an increased risk of atherosclerosis, coronary artery disease, and stroke. Additionally, altered methylation processes influence neurological function, with associations reported between this polymorphism and cognitive decline, neurodegenerative diseases, and psychiatric disorders.
Genetic testing for the SHMT1 C1240T polymorphism provides insight into an individual’s predisposition to altered folate metabolism, homocysteine-related disorders, and DNA methylation imbalances. Identifying this variant allows for assessing one-carbon cycle efficiency, nucleotide synthesis capacity, and potential risks associated with neural tube defects, cardiovascular diseases, and cancer, contributing to a deeper understanding of genetic influences on cellular methylation and metabolic health.
The SHMT1 C1240T polymorphism genetic test is also included in:
