Sorted By Test Name - Mayo Medical Laboratories

MTHFR
81648
MTHFR C677T Mutation Analysis, Blood
Clinical Information: Hyperhomocysteinemia is an independent risk factor for coronary artery
disease (CAD), acute myocardial infarction (MI), peripheral arterial disease, stroke, and venous
thromboembolism. Homocysteine is a sulfhydryl-containing amino acid formed as an intermediary during
the conversion of methionine to cystathionine. Genetic or nutrition-related disturbances (eg, deficiency of
vitamins B12, B6, or folic acid) may impair the transsulfuration or remethylation pathways of
homocysteine metabolism and cause hyperhomocysteinemia. The enzyme 5,10-methylenetetrahydrofolate
reductase (MTHFR) catalyzes reduction of 5,10-methylenetetrahydrofolate to 5-methyltetrahydrofolate,
the major form of folate in plasma. 5-Methyltetrahydrofolate serves as a methyl donor for remethylation
of homocysteine to methionine. Patients with severe MTHFR deficiency (enzymatic activity 0%-20% of
normal) develop homocystinuria, a severe disorder with a wide range of associated clinical
manifestations, including developmental delay, mental retardation, and premature vascular disease.
Several unique MTHFR gene mutations have been associated with homocystinuria, all among patients
who were either homozygous or compound heterozygotes for 1 or more of these mutations. MTHFR
C677T, a milder deficiency of MTHFR, with approximately 50% residual enzyme activity and marked
enzyme lability to heat inactivation, is associated with a cytosine to thymine mutation at nucleotide
position C677->T, encoding for an alanine-223 to valine substitution. This mutation is quite common,
with an allelic frequency of 31% to 39% (homozygote frequency =9%-17%) among the Caucasian North
American population. Homozygosity for the mutant allele confers a markedly increased risk of
hyperhomocysteinemia when vitamin deficiency is present, especially folic acid. Heterozygosity for the
mutation appears to confer less risk for hyperhomocysteinemia and may not warrant intervention. The
weight of current evidence suggests that the MTHFR C677T mutation is not an independent risk factor for
CAD in the absence of hyperhomocysteinemia; data is not available for the risk of venous
thromboembolism conveyed by the MTHFR C677T mutation. At this time, the utility of direct mutation
analysis for the MTHFR C677T mutation in an asymptomatic family member with a normal basal
homocysteine level is unknown. Folic acid supplementation can reduce blood homocysteine levels to
normal. For patients with suspected hyperhomocysteinemia, we recommend measurement of basal plasma
homocysteine levels (HCYSP/80379 Homocysteine, Total, Plasma). Vitamin B12, B6, and folic acid
levels should be measured in patients with hyperhomocysteinemia.
Useful For: Direct mutation analysis for the 5,10-methylenetetrahydrofolate reductase (MTHFR)
C677T gene mutation in patients with coronary artery disease, acute myocardial infarction, peripheral
vascular artery disease, stroke, or venous thromboembolism who have increased basal homocysteine
levels or an abnormal methionine load test
Interpretation: The interpretive report will include specimen information, assay information,
background information, and conclusions based on the test results.
Reference Values:
Negative
Clinical References: 1. Rees MM, Rodgers GM: Homocysteinemia: association of a metabolic
disorder with vascular disease and thrombosis. Thromb Res 1993 September 1;71(5):337-359 2. Frosst P,
Blom HJ, Milos R, et al: A candidate genetic risk factor for vascular disease: a common mutation in
methylenetetrahydrofolate reductase. Nat Genet 1995 May;10(1):111-113 3. Kluijtmans LA, van den
Heuvel LP, Boers GH, et al: Molecular genetic analysis in mild hyperhomocysteinemia: a common
mutation in the methylenetetrahydrofolate reductase gene is a genetic risk factor for cardiovascular
disease. Am J Hum Genet 1996 January;58(1):35-41 4. Ma J, Stampfer MJ, Hennekens CH, et al:
Methylenetetrahydrofolate reductase polymorphism, plasma folate, homocysteine, and risk of myocardial
infarction in US physicians. Circulation 1996 November 15;94(10):2410-2416 5. Deloughery TG, Evans
A, Sadeghi A, et al: Common mutation in methylenetetrahydrofolate reductase. Correlation with
homocysteine metabolism and late-onset vascular disease. Circulation 1996 December
15;94(12):3074-3078 6. Christensen B, Frosst P, Lussier-Cacan S, et al: Correlation of a common
mutation in the methylenetetrahydrofolate reductase gene with plasma homocysteine in patients with
coronary disease. Arteroscler Thromb Vasc Biol 1997 March;17(3):569-573
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