DESCRIPTION: Genetic testing for polymorphisms: MTHFR; MTR; MTRR; COMT; AHCY
MTHFR C677T
MTHFR A1298C
MTR C3518T
MTR A27656G
MTRR A66G
COMT G472A
COMT G304A
AHCY g.G32878481C
AHCY C112T
AHCY G367A
Mutations in the polymorphic sites of these genes are associated with:
Cardiovascular disease (including coronary artery disease, stroke and blood clots)
Peripheral neuropathy, congenital birth defects, neural tube defects (spina bifida) and miscarriages.
Chronic disease, e.g. fibromyalgia, chronic fatigue syndrome, migraines, IBS (irritable bowel syndrome), dementia, OCD, bipolar syndrome, schizophrenia, depression and more.
Diminished methylation capacities of DNA, phytochemicals, catecholamines, environmental toxins (xenobiotics)
COLLECTION Whole blood in sodium citrate tube or buccal swab
SPECIMEN STABILITY Stable at room temperature for 1 week
REJECTION CRITERIA Blood sample over 1 week old; grossly hemolyzed, icteric, and lipemic specimens; improper anticoagulant used
Real-time SSP-PCR (Polymerase Chain Reaction using Sequence Specific Primers) followed by melt curve analysis
Presence or absence of the mutations is reported. Homozygosity (both copies of the gene contain the mutation) or heterozygosity (only one of two copies of the gene contains the mutation) of each mutation is reported for the affected individuals. Effect on the enzyme activity associated with each combination of genotypes is reported along with personalized supplementation recommendations based on the results.
Homocysteine and MTHFR C677T polymorphism in children and adolescents with psychotic and mood disorders. Kevere L, Purvina S, Bauze D, Zeibarts M, Andrezina
R, Piekuse L, Brekis E, Purvins I. Nord J Psychiatry. 2013 Apr 16
Hyperhomocysteinemia and of Methylenetetrahydrofolate Reductase (C677T) Genetic Polymorphism in Patients with Deep Vein Throm bosis. Brezovska-Kavrakova
J, Krstevska M, Bosilkova G, Alabakovska S, Panov S, Orovchanec N. Mater Sociomed. 2013;25(3):170-4. doi: 10.5455/msm.2013.25.170-174. Genetic polymorphisms and the risk of myocardial infarction in patients under 45 years of age.
Sakowicz A, Fendler W, Lelonek M, Sakowicz B, Pietrucha T. Biochem Genet. 2013 Apr;51(3-4):230-42. doi: 10.1007/s10528-012-9558-5.
Lewis SJ, Lawlor DA, Davey Smith G, et al. (2006). "The thermolabile variant of MTHFR is associated with depression in the Br itish Women's Heart and Health Study
and a meta-analysis". Mol. Psychiatry 11 (4): 352–60. doi:10.1038/sj.mp.4001790. PMID 16402130.
Maternal and infant gene-folate interactions and the risk of neural tube defects. Etheredge AJ, Finnell RH, Carmichael SL, Lammer EJ, Zhu H, Mitchell LE, Shaw GM. Am J Med Genet A. 2012 Oct;158A(10):2439-46. doi: 10.1002/ajmg.a.35552.
Methylenetetrahydrofolate reductase polymorphism affects the change in homocysteine and folateconcentrations resulting from low dose folic acid supplementati on in women with unexplained recurrent miscarriages. Nelen WL, Blom HJ, Thomas CM, Steegers EA, Boers GH, Eskes TK. J Nutr. 1998 Aug;128(8):1336-41.
Schwahn B, Rozen R (2001). "Polymorphisms in the methylenetetrahydrofolate reductase gene: clinical consequences". Am J Pharm acogenomics 1 (3): 189–201. doi:10.2165/00129785-200101030-00004. PMID 12083967.
David Watkins et al.: Hyperhomocysteinemia due to Methionine Synthase Deficiency, cblG: Structure of the MTR Gene, Genotype Diversity, and Recognition of a Common Mutation, P1173L. Am. J. Hum. Genet. 71:143-153, 2002.
Ma’atem B. Fofou-Caillierez et al.: Interaction between methionine synthase isoforms and MMACHC: characterization in cblg-variant, cblG and cblC inherited causes of megaloblastic anaemia. Human Molecular Genetics, 2013
Sheila Dawling et al.: Catechol-O-Methyltransferase (COMT)-mediated Metabolism of catechol Estrogens: Comparison of Wild-Type and variant COMT Isoforms. CANCER RESEARCH 61, 6716-6722, September 15, 2001.
James D. Yager. Catechol-O-methyltransferase: characteristics, polymorphisms and role in breast cancer. Drug Discov Today Dis Mech.; 9(1-2)2012.
Ercole L.Cavalieri et al.: Catechol ortho-quinones: the electrophilic compounds that form depurinating DNA adducts and could initiate cancer and other diseases. Carcinogenesis vol.23 no 6 pp.1071-1077, 2012.
Xiang Tan and Minhwu Chen. Association between Catechol-O-methyltransferase rs4680 (G>A) polymorphism and lung cancer risk. Diagnostic Pathology, 9:192, 2014
Seong-Gene Lee et al.: Association of Ala72Ser polymorphism with COMT enzyme activity and the risk of schizophrenia in Koreans. Hum Genet, 116: 319-328, 2005.
G. Lin et al.: Contribution of catechol-O-methyltransferase Val158Met polymorphism to endometrial cancer risk in postmenopausal women: a meta-analysis. Genetics and Molecular Research 12 (4): 6442-6453, 2013
David Watkins & David S. Rosenblatt. Update and new concepts in vitamin responsive disorders of folate transport and metabolism. J Inherit Metab Dis, DOI 10.1007/s10545-011-9418-1, 2011
Mojgan Hosseini: Role of Polymorphism of Methyltetrahydrofolate-Homocysteine Methyltransferase (MTR) A275G and Breast Cancer Risk. POL J PATHOL ; 64 (3): 191-195, 2013
Beetstra S. et al.: Methionine-dependence phenotype in the de novo pathway in BRCA1 and BRCA2 muataion carriers with and withpout breast cancer. Cancer Epidemiol Biomarkers Prev; 17: 2565-2571, 2008
Nishi Gutpa et al.: Significant Impact of the MTHFR Polymorphisms and Haplotypes on Male Infertility Risk. Plos One, Volume 8, Issue 7, July 2013.
Moshin Yakub et al.: Significant Impact of the MTHFR Polymorphisms and Haplotypes on Male Infertility Risk. Plus One, Volume 7, Issue 3, March 2012.
Jane C. Figueiredo et al.: Global DNA Hypomethylation (LINE-1) in the Normal Colon and Lifestyle Characteristics, Dietary and Genetic Factors. Cancer Epidemiol Biomarkers Prev., 18(4): 1041-1049, April 2009.
Daijun Zhou et al.: The Polymorphisms in Methylenetetrahydrofolate Reductase, Methionine Synthase, Methionine Synthase Reductase, and the Risk of Colorectal Cancer. Int. J. Biol. Sci. 8(6):819-830, 2012
References:
David Watkins et al.: Hyperhomocysteinemia due to Methionine Synthase Deficiency, cblG: Structure of the MTR Gene, Genotype Diversity, and Recognition of a Common Mutation, P1173L. Am. J. Hum. Genet. 71:143-153, 2002.
Sheila Dawling et al.: Catechol-O-Methyltransferase (COMT)-mediated Metabolism of catechol Estrogens: Comparison of Wild-Type and variant COMT Isoforms. CANCER RESEARCH 61, 6716-6722, September 15, 2001.
Ercole L.Cavalieri et al.: Catechol ortho-quinones: the electrophilic compounds that form depurinating DNA adducts and couldinitiate cancer and other diseases. Carcinogenesis vol.23 no 6 pp.1071-1077, 2012.
Xiang Tan and Minhwu Chen. Association between Catechol-O-methyltransferase rs4680 (G>A) polymorphism and lung cancer risk. Diagnostic Pathology, 9:192, 2014
Seong-Gene Lee et al.: Association of Ala72Ser polymorphism with COMT enzyme activity and the risk of schizophrenia in Koreans. Hum Genet, 116: 319-328, 2005.
David Watkins & David S. Rosenblatt. Update and new concepts in vitamin responsive disorders of folate transport and
metabolism. J Inherit Metab Dis, DOI 10.1007/s10545-011-9418-1, 2011
Jane C. Figueiredo et al.: Global DNA Hypomethylation (LINE-1) in the Normal Colon and Lifestyle Characteristics, Dietary and Genetic Factors. Cancer Epidemiol Biomarkers Prev., 18(4): 1041-1049, April 2009.
Daijun Zhou et al.: The Polymorphisms in Methylenetetrahydrofolate Reductase, Methionine Synthase, Methionine Synthase Reductase, and the Risk of Colorectal Cancer. Int. J. Biol. Sci. 8(6):819-830, 2012
Moll S., et al.: Homocysteine and MTHFR Mutations. Circulation. 132:e6-e9, 2015.
Cotton F., et al.: Reference Intervals for Plasma Homocysteine by the AxSYM Immunoassay after Collection in Fluoride tubes. Clinical Chemistry 49, No.2, 2003.
Rasmussen K., et al.: Age- and gender- specific reference intervals for total homocysteine and methylmalonic acid in plasma before and after vitamin supplementation. Clinical Chemistry 42:4, 630-636, 1996.
Faure-Delanef L., et al.: Methylenetetrahydrofolate Reductase Thermolabile variant and Human Longevity. Am. J.Hum. Genet., 60:999 -1001, 1997.
M.R Nehler, L.M Taylor Jr, J.M Porter. Homocysteinemia as a risk factor for atherosclerosis: a review. Cardiovascular Surgery Volume 5, Issue 6, December, Pages 559-561,1997.
