attomol^® MTHFR 1298A>C Quicktype

MTHFR catalyzes the irreversible reduction of 5,10-methylenetetrahydrofolate to 5-methyltetrahydrofolate, which is essential for folate-mediated carbon metabolism [1][2][3]. Folate plays an important role in numerous metabolic processes that can affect DNA synthesis and is involved in DNA and protein methylation [2][3]. Disruption of folate metabolism can lead to hyperhomocysteinemia (Hcy), which is associated with an increased risk of many diseases, including birth defects, pregnancy complications, vascular and neurodegenerative diseases, diabetes, neuropsychiatric disorders, cancers, heart disease, and thombosis [4][5]. Accumulation of homocysteine in the plasma may be caused by the mutation MTHFR 677C>T resulting in a thermolabile enzyme with reduced activity [6]. In the context of an increased homocysteine level, another polymorphism of the MTHFR gene (MTHFR 1298A>C) is discussed. If this mutation occurs alone, it appears to have no effect on the homocystein plasma concentration. However, it has been shown that patients who are heterozygous for both polymorphism have decreased MTHFR enzyme activity by 50 %, increased homocysteine concentrations and reduced folate levels [7][8]. In consequence, especially in patients who carriers the MTHFR 677T allele, it is useful to determine the MTHFR 1298 genotype in the diagnosis of cardiovascular diseases, as well as other genetic risk factors [4].
The determination of the MTHFR 1298 mutation should not be used as a screening test, since the mutation can generally be present in both diseased and healthy individuals. Furthermore, the American College of Medical Genetics and the American College of Obstetricians and Gynecologists discourage determination in pregnant women and in cases of repeated pregnancy loss [10][11].
Genetic determination of the MTHFR 1298 mutation can be used to confirm the diagnosis of inherited hyperhomocysteinemia due to MTHFR deficiency and, if necessary, infer association with other resulting vascular diseases such as thrombosis [10].

Prevalence
The 1298A>C mutation is present in Caucasians in heterozygous form in up to 40 %, the homozygous form in about 4 % of the population [9]. The ESVS guideline states that the MTHFR polymorphism with hyperhomocysteinemia has a prevalence of 5 % in the general population and 10 % in VTE (venous thromboembolism) patients. They therefore describe the relative risk of first VTE due to the polymorphism compared to controls as 1.5 [12].

[1] Fowler B: The Folate cycle and disease in humans. Kidney International 2001, 59(78):221-229.
[2] Sharp L. et al.: Polymorphisms in genes involved in folate metabolism and colorectal neoplasia: A HuGE review. Am J Epidemiol. 2004, 159(5):423-443.
[3] Zhou S. et al: Notable epigenetic role of hyperhomocysteinemia in atherogenesis. Lipids in Health and Disease 2014, 13:134.
[4] Födinger M. et al.: Molecular biology of 5,10-methylenetetrahydrofolate reductase. J.Nephrol. 2000, 13, 20-33.
[5] Brustolin S. et al.: Genetics of homocysteine metabolism and associated disorders. Brazilian J Med Biol Res. 2010, 43(1):1-7.
[6] Dean: Methylenetetrahydrofolate Reductase Deficiency. 2012 Mar 8 [updated 2016 Oct 27]. In: Pratt V. M. et al., editors. Medical Genetics Summaries [Internet]. Bethesda (MD): National Center for Biotechnology Information (US).
[7] Födinger M. et al.: Recent insights into the molecular genetics of the homocysteine metabolism. Kidney Int. Suppl., 2001, 78, 238-242.
[8] Weisberg I. S. et al.: The 1298A>C polymorphism in methylenetetrahydrofolate reductase (MTHFR): in vitro expression and association with homocysteine. Atherosclerosis, 2001, 156, 409-415.
[9] Peng F. et al.: Single nucleotides polymorphisms in the methylenetetrahydofolate reuctase gene are common in US Causasia and Hispanic American populations. Int.J.Mol.Med., 2001, 8, 509-511.
[10] The American College of Obstetricians and Gynecologists: Practice Bulletin, Inherited Thrombophilias in Pregnancy. Clinical Management Guidelines for Obstetrician-Gynecologists. 2018, 132(1):e18-e34.
[11] Grody et al.: ACMG Factor V. Leiden Working Group. American College of Medical Genetics consensus statement on factor V Leiden mutation testing. Genet Med. 2001, 3(2):139-48.
[12] European Society for Vascular Surgery (ESVS): Clinical Practice Guidelines on the Management of Venous Thrombosis. Eur J Vasc Endovasc Surg, 2021, 61: 9-82.

• PCR-H₂O
• PCR-buffer I
• Primer MTHFR 1298A>C
• instructions for use

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