Laboratory for Molecular Diagnostics
Center for Nephrology and Metabolic Disorders

Methylenetetrahydrofolate reductase

The MTHFR gene encodes an important enzyme in the metabolism of sulfur-containing amino acids. Mutations to a variable degree lead to hyperhomocysteinemia with several cardio-vascular consequences, including coronary heart disease and thrombosis. Homocysteinuria is an autosomal recessive disorder caused by loss of function mutations.

Epidemiology

The frequency of homozygous C677T mutation in Caucasian population is about 4-10% a heterozygous state is found in about 40-50%. There is a gradient in frequency from North to South.

Gene Structure

Then gene MTHFR is about 3kb in size. Its locus is on chromosome 1 (1p36.3). It consists of 11 exons.

Phenotype

Hyperhomocysteinemia is discussed as a cause of accelerated arteriosclerosis. Thrombophilia seems to be associated with MTHFR mutations too. In dialysis patients there is the homocysteine level elevated partly due to uremia and further increased by MTHFR mutations. Folic acid substitution can decrease this level and this might be associated with a lover risk for cardiovascular diseases.

Pathology

The enzyme methylenetetrahydrofolate reductase is important to the metabolism of the amino acid cysteine. A mutation in this gene leads to elevation of the homocysteine level in plasma.

Test Strategy

Patient with higher risk for cardiovascular disease to decide folic acid substitution. This test is much easier to perform than measuring homocysteine levels in plasma.

Interpretation

Carriers of this mutation have a greater risk for cardiovascular diseases and could be treated with folic acid.

Genetests:

Clinic Method Carrier testing
Turnaround 5 days
Specimen type genomic DNA
Clinic Method Massive parallel sequencing
Turnaround 25 days
Specimen type genomic DNA
Clinic Method Genomic sequencing of the entire coding region
Turnaround 25 days
Specimen type genomic DNA
Clinic Method Target mutation analysis
Turnaround 5 days
Specimen type genomic DNA
Research Method Multiplex Ligation-Dependent Probe Amplification
Turnaround 25 days
Specimen type genomic DNA

Related Diseases:

Thromboembolic diseases
Autosomal dominant protein C deficiency
PROC
Autosomal dominant protein S deficiency
PROS1
Autosomal recessive protein C deficiency
PROC
Autosomal recessive protein S deficiency
PROS1
F2
F5
Factor XII deficiency
F12
HABP2
Hyperhomocysteinemic thrombosis
CBS
Hypoplasminogenemia
Dysplasminogenemia
PLG
Hypoplasminogenemia
PLG
MTHFR
PAI transcription modulator
SERPINE1
Protein Z deficiency
PROZ
SERPINA10
SERPINC1
THBD
Thrombophilia due to heparin cofactor 2 deficiency
SERPIND1
VKORC1
Arteriosclerosis
APOB
APOE
HABP2
LDLR
LPA
MTHFR
PON1
SLC3A1
Membranoproliferative glomerulonephritis (MPGN)
ADAMTS13
C1QA
C1QB
C1QC
C3
CD46
CFB
CFD
CFH
CFHR1
CFHR2
CFHR3
CFHR4
CFHR5
CFI
CLU
CR1 deficiency
CR1
Complement component C1q deficiency
C1QA
C1QB
C1QC
Complement component C1s deficiency
C1S
DGKE
PIGA
THBD

References:

1.

Pallaud C et al. (2001) Candidate gene polymorphisms in cardiovascular disease: a comparative study of frequencies between a French and an Italian population.

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2.

Peng F et al. (2001) Single nucleotide polymorphisms in the methylenetetrahydrofolate reductase gene are common in US Caucasian and Hispanic American populations.

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3.

Födinger M et al. (1997) Mutation (677 C to T) in the methylenetetrahydrofolate reductase gene aggravates hyperhomocysteinemia in hemodialysis patients.

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4.

Orphanet article

Orphanet ID 123529 [^]
5.

NCBI article

NCBI 4524 [^]
6.

OMIM.ORG article

Omim 607093 [^]
7.

Wikipedia article

Wikipedia EN (Methylenetetrahydrofolate_reductase) [^]
Update: April 29, 2019