Methylenetetrahydrofolate Reductase (MTHFR) Genotyping
Test Code
MTHFR
CPT Codes
83891-3F x1; 83892-3F x2; 83900-3F x1; 83914-3F x2; 83909-3F x1; 83912-3F x1; 83912-25 x1
Specimen
Whole blood or buccal swabs
Volume
5 mL of whole blood or four buccal swabs
Minimum Volume
3 mL of whole blood or four buccal swabs
Container
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
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.
.Limitations
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.
Methodology
Multiplex polymerase chain reaction and allele specific primer extension (Tag-It [TM]).
Turnaround Time
Five business days after receipt of specimen. STAT turnaround time of 3 business days is available for an additional charge.
References
Kolling K et al. Methylenetetrahydrofolate reductase gene C677T and A1298C polymorphisms, plasma homocysteine, folate, and vitamin B12 levels and the extent of coronary artery disease. Am J Cardiol 2004; 93:1201-1206.
Toffoli G et al. Effect of methylenetetrahydrofolate reductase 677C>T polymorphism on toxicity and homocysteine plasma level after chronic methotrexate treatment of ovarian cancer patients. Int J cancer 2003; 103:294-299.
Strunk T et al. Subacute leukoencephalopathy after low-dose intrathecal methotrexate in an adolescent heterozygous for the MTHFR C677T polymorphism. Med Pediatr Oncol 2003; 40:48-50.
Kottke-Marchant K. Genetic Polymorphisms Associated With Venous and Arterial Thrombosis: An Overview. Arch Pathol Lab Med 2002; 126(3):295-304.
van Ede AE et al. The C677T mutation in the methylenetetrahydrofolate reductase gene: a genetic risk factor for methotrexate-related elevation of liver enzymes in rheumatoid arthritis patients. Arth Rheum 2001; 44(11):2525-2530.
Ulrich CM et al. Pharmacogenetics of methotrexate: toxicity among marrow transplantation patients varies with the methylenetetrahydrofolate reductase C677T polymorphism. Blood 2001; 96(1):231-234.
Weisberg IS et al. The 1298A-->C polymorphism in methylenetetrahydrofolate reductase (MTHFR): in vitro expression and association with homocysteine. Atherosclerosis 2001; 156(2):409-415.
Lievers KJ et al. A second common variant in the methylenetetrahydrofolate reductase (MTHFR) gene and its relationship to MTHFR enzyme activity, homocysteine, and cardiovascular disease risk. J Mol Med 2001; 79(9):522-8.
Botto LD and Yang Q. 5,10-Methylenetetrahydrofolate reductase gene variants and congenital anomalies: a HuGE review. Am Epidemiol 2000; 151(9):862-876.
Weisberg I et al. A second genetic polymorphism in methylenetetrahydrofolate reductase (MTHFR) associated with decreased enzyme activity. Mol Genet Metab 1998; 64:169-172.
Kang SS et al. Thermolabile defect of methylenetetrahydrofolate reductase in coronary artery disease. Circulation 1993; 8(4 Pt 1):1463-9.