Methylenetetrahydrofolate Reductase (MTHFR) Genotyping

Test Code

CPT Code

Whole blood or buccal swabs

5 mL of whole blood or four buccal swabs 

Minimum Volume
3 mL of whole blood or four buccal swabs 

Lavender-stopper (EDTA) tube or paper envelope for dried buccal swabs 

Storage Instructions
Maintain at room temperature or refrigerate

Cause for Rejection
Hemolyzed specimen; quantity not sufficient

General Purpose and Use
The MTHFR (Methylenetetrahydrofolate Reductase) enzyme catalyzes the formation of 5-methyltetrahydrofolate, the major circulating form of active folate.  Absence of active folate leads to accumulation of plasma homocysteine.  The 677 C>T polymorphism of MTHFR leads to decreased MTHFR enzymatic activity and elevated homocysteine.  The 1298 A>C polymorphism is associated with significant increases plasma homocysteine levels only when in combination with the 677 C>T polymorphism.   Elevated plasma homocysteine has been shown to be a risk factor for atherosclerotic heart disease, myocardial infarction, cerebrovascular disease, and venous thrombosis.  Additionally, associations between the 677 C>T polymorphism and increased risk for methotrexate toxicity, increased chemosensitivity of colon and breast cancers to 5-fluorouracil, and increased risk of fetal neural tube defects in pregnant women have also been reported, although these associations remain controversial.

Alleles Detected:

Other genetic variants of the MTHFR gene that are not detected in the assay may influence MTHFR enzymatic activity.  Other genetic and non-genetic factors may also influence plasma folate and homocysteine levels, and the balance of proper coagulation.

Real-time polymerase chain reaction with fluorescence detection.

For a PDF version, click here.