The MTHFR gene (Methylenetetrahydrofolate Reductase) provides instructions for making an enzyme that processes folate (Vitamin B9). Variations in this gene, often called mutations or polymorphisms, are common in the general population. These inherited genetic differences affect how efficiently the enzyme works. Carrying a variation can reduce the body’s capacity to convert folate into its active, usable form.
The MTHFR Gene’s Function
The MTHFR enzyme participates in the body’s one-carbon metabolism, a pathway involved in processes like DNA synthesis. The enzyme catalyzes a step in the folate cycle, converting 5,10-methylenetetrahydrofolate into 5-methyltetrahydrofolate (5-MTHF), the active form of folate.
The active 5-MTHF is then used in remethylation to convert the amino acid homocysteine into methionine. Methionine is necessary for producing S-adenosylmethionine (SAM), which acts as the primary methyl donor for many chemical reactions, including those regulating gene expression.
When MTHFR enzyme function is reduced by a genetic variant, this conversion step slows down. This decreased production of 5-MTHF reduces the amount of homocysteine converted to methionine. This can result in elevated levels of homocysteine in the blood, known as hyperhomocysteinemia, which is studied as a possible risk factor for various health conditions.
Understanding the Key MTHFR Variants
Two single-nucleotide polymorphisms (SNPs) are studied most frequently: C677T and A1298C. The C677T variant involves a change from cytosine (C) to thymine (T) at position 677. This change creates a thermolabile enzyme, meaning its activity is reduced.
The A1298C variant involves a change from adenine (A) to cytosine (C) at position 1298. This variant results in a less pronounced reduction in enzyme activity compared to C677T. Since individuals inherit one copy of the MTHFR gene from each parent, the combination of these copies determines the reduction in enzyme activity.
A person is heterozygous if they have one variant copy and one normal copy (e.g., C/T for C677T). A person is homozygous if they have two variant copies (e.g., T/T for C677T). For the C677T variant, the heterozygous C/T genotype typically results in roughly 35% reduced enzyme activity. The homozygous T/T genotype can reduce activity by 60% to 70%.
How Genetic Testing Is Performed
Testing for MTHFR variants analyzes a person’s DNA to identify nucleotide changes at the C677T and A1298C positions. Sample collection varies by provider. Standard clinical tests often require a blood sample drawn at a clinic.
Some specialized labs and direct-to-consumer services offer at-home collection using a cheek swab or saliva sample. The collected sample contains the DNA necessary for analysis. Once received, the lab extracts the DNA and analyzes it using methods like Polymerase Chain Reaction (PCR) to determine the exact genotype.
The cost of MTHFR testing typically ranges from $100 to $300, depending on if it is a standalone test or part of a larger genetic panel. Insurance coverage is variable and often depends on whether a healthcare provider deems the test medically necessary. Results are usually available within five to seven business days.
Making Sense of Your Test Results
The results report uses specific notation to indicate the variant alleles found for the C677T and A1298C locations. The C/C and A/A genotypes represent the wild-type, or normal, version of the gene, associated with full enzyme activity.
The possible results for C677T are C/C, C/T, or T/T. For A1298C, results are A/A, A/C, or C/C. The C/T or A/C notation indicates a heterozygous state, meaning one variant copy was inherited. The T/T or C/C notation signifies a homozygous state, where both copies carry the variant.
Another element is that individuals can be “compound heterozygous,” meaning they have one variant copy of C677T (C/T) and one variant copy of A1298C (A/C). The specific genotype found is directly linked to the estimated reduction in enzyme activity. For instance, the T/T result for C677T is associated with the largest reduction in function, potentially 70% less than the normal C/C genotype. A compound heterozygous result is also associated with a significant decrease in activity, estimated to be around 55% less than normal. A positive test indicates a genetic predisposition, not a guarantee of a health problem.
Practical Steps Following a Diagnosis
A result indicating one or more MTHFR variants prompts management strategies to support the methylation pathway. A primary focus is optimizing folate intake, as the variant reduces the efficiency of converting folate into its active form. This often involves adjusting the form of Vitamin B9 consumed in supplements.
Many supplements contain folic acid, the synthetic form of folate that requires the MTHFR enzyme for conversion into active L-methylfolate. Since the variant enzyme struggles with this conversion, the recommended approach is often to use L-methylfolate directly. Supplementing with this biologically active form effectively bypasses the impacted conversion step.
Consulting a healthcare provider, such as a genetic counselor or a physician familiar with nutrigenomics, is an important next step. These professionals can interpret the test results within the context of overall health and diet. They may also recommend dietary adjustments to ensure sufficient intake of naturally occurring folates and other B vitamins.