MTHFR Genotype Test (840)

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CPT Code:


Test Type: Whole Blood Kit Based
Stability Time:


Room temperature or Refrigerated (2-8 C) for 14 days

Reference Range:
  • Normal:
    • 677 C/C 1298 A/A
  • 1-2 Copies of Variant:
    • 677 C/T 1298 A/A
    • 677 C/C 1298 A/C
    • 677 C/T 1298 A/C
    • 677 C/C 1298 C/C
    • 677 C/T 1298 C/C
  • Significant Variant:
    • 677 T/T 1298 A/A
    • 677 T/T 1298 A/C
    • 677 T/T 1298 C/C


MTHFR (methylenetetrahydrofolate reductase) is the enzyme responsible for metabolizing folate methyl folate which, in turn, is essential for converting homocysteine to methionine. Genetic variations in the MTHFR enzyme at the 677 and 1298 positions can affect this step and serum homocysteine levels. Homocysteine is a necessary amino acid that plays an important role in metabolism, but high levels are related to a higher risk of cardiovascular disease (CVD), especially stroke.1

Moreover, when high levels of homocysteine (>15 µmol/L) are coupled with the MTHFR 677 T/T variant there is an even higher risk of stroke. 2

Other MTHFR genotypes may also be associated with increased stroke risk.2 Recent meta-analyses indicate clear associations of MTHFR genotypes 677 T/T, 677 C/T, 1298 A/C and 1298 C/C with increased risk of stroke.2-4

Individuals with the MTHFR 677 T/T genotype may require supplementation with methyl folate instead of folate to adequately lower their homocysteine levels. Lowering homocysteine in patients with either known CVD or hypertension using either the combination of daily 2.5 mg of folic acid, 50 mg of vitamin B6, and 1 mg of vitamin B12 or 0.8 mg of folate per day has been shown to significantly reduce the risk of stroke.5-6 There are two common variants of MTHFR associated with CVD risk (C677T and A1298C). Population frequencies of these variants are: 677 C/C (48%) 677 C/T (41%) 677 T/T (11%) 1298 A/A (48%) 1298 C/C (10%) 1298 A/C (42%) A/C or C/C genotypes are mild variants but when they occur together with either 677 C/T or T/T they are significant variants associated with increased homocysteine levels.

MTHFR interpretation is in accordance with recently published data.

References: He Y, Li Y, Chen Y, Feng L, Nie Z. Homocysteine level and risk of different stroke types: a meta-analysis of prospective observational studies. Nutr Metab Cardiovasc Dis. 2014;24(11):1158-1165. Li P, Qin C. Methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms and susceptibility to ischemic stroke: a meta-analysis. Gene. 2014;535(2):359-364. Zhang MJ, Hu ZC, Yin YW, et al. A meta-analysis of the relationship between MTHFR gene A1298C polymorphism and the risk of adult stroke. Cerebrovasc Dis. 2014;38(6):425-432. Kang S, Wu Y, Liu L, Zhao X, Zhang D. Association of the A1298C polymorphism in MTHFR gene with ischemic stroke. J Clin Neurosci. 2014;21(2):198-202. Saposnik G, Ray JG, Sheridan P, McQueen M, Lonn E; Heart Outcomes Prevention Evaluation 2 Investigators. Homocysteine-lowering therapy and stroke risk, severity, and disability: additional findings from the HOPE 2 trial. Stroke. 2009;40(4):1365-1372.

Methodology - Real-time polymerase chain reaction (RT-PCR)

Collection Details:

Collection Instructions:

Preferred Specimen

1.0 mL blood collected in a K2 EDTA whole blood tube (lavender top)

Transport Temperature

Refrigerated (ship on frozen cold packs)