Methlyenetetrahydrofolate reductase (MTHFR) is a key enzyme in the metabolism of folic acid and homocysteine. The Iverson MTHFR test detects two common variants in the genes that code MTHFR. Both variants are associated decreases in MTHFR activity and increase the risk of elevated homocysteine levels. Hyperhomocysteinemia is associated with a growing list of serious health concerns. A simple blood test indentifies which patients have these genetic variations. This information can lead to important preventative and therapeutic steps.

MTHFR

• The C677T variant extremely common: 13% of the general population are homozygous and 42% are heterozygous1
• The A1298C variant is present 30% of Caucasians, 20% of Asians, and 16% of African americans2
• American Hispanics had a higher incidence of C677T and A1298C than those reported in Caucasians3
• A1298C and C677T are both associated with decreased MTHFR activity and elevated levels of homocysteine4
• Elevated homocysteine levels are associated with cardiovascular disease including atherosclerosis and thrombosis4
• A1298C and C677T are associated with neural tube defects5, recurrent miscarriages6, and autism7
  
• A1298C and C677T have been shown to increase the risk of depression, bipolar disorder, and schizophrenia8
• C677T can increase the risk for breast cancer9

1. 1. Botto L, Yang Q. 5,10-Methylenetetrahydrofolate reductase gene variants and congenital anomalies: a HuGE review. Am J Epidemiol 2000;151:862–877.
2. 2. Langman LJ, Wong BYL, Boggis C, Rubin LA, Cole DEC (1998) The prevalence and linkage disequilibrium of three methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms varies in different ethnic groups. Paper presented at INABIS '98–5th Internet World Congress on Biomedical Sciences at McMaster University, Hamilton, Ontario, December 7–16.
3. 3. Chowdary D, Streck D, Schwalb MN, Dermody JJ. High Incidence of Two Methylenetetrahydrofolate Reductase Mutations (C677T and A1298C) in Hispanics. Genetic Testing. 2003, 7(3): 255-257.
4. 4. Kolling K, Ndrepepa G, Koch W, Braun S, Mehilli J, Schomig A, Kastrati A. 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;10:1201–1206.
5. 5. van der Put NM, van Straaten HW, Trijbels FJ, Blom HJ. Folate, homocysteine and neural tube defects: an overview. Exp Biol Med (Maywood). 2001 Apr;226(4):243-70.
6. 6. N Mtiraoui, W Zammiti, L Ghazouani, N J. Braham, S Saidi, R R Finan, W Y Almawi, and T Mahjoub Methylenetetrahydrofolate reductase C677T and A1298C polymorphism and changes in homocysteine concentrations in women with idiopathic recurrent pregnancy losses. Reproduction, February 1, 2006; 131(2): 395 - 401.
7. 7. James SJ, et al. Metabolic endophenotype and related genotypes are associated with oxidative stress in children with autism. Am J Med Genet B Neuropsychiatr Genet. 2006 Dec 5;141(8):947-56.
8. 8. Gilbody S, Lewis S, Lightfoot T. Methylenetetrahydrofolate reductase (MTHFR) genetic polymorphisms and psychiatric disorders: a HuGE review. Am J Epidemiol. 2007 Jan 1;165(1):1-13. Epub 2006 Oct 30.
9. 9. Shrubsole MJ, et al. MTHFR polymorphisms, dietary folate intake, and breast cancer risk: results from the Shanghai Breast Cancer Study. Cancer Epidemiol Biomarkers Prev. 2004 Feb;13(2):190-6.