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.
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.
Then gene MTHFR is about 3kb in size. Its locus is on chromosome 1 (1p36.3). It consists of 11 exons.
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.
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.
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.
Carriers of this mutation have a greater risk for cardiovascular diseases and could be treated with folic acid.
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 |
1. |
Pallaud C et al. (2001) Candidate gene polymorphisms in cardiovascular disease: a comparative study of frequencies between a French and an Italian population. |
2. |
Peng F et al. (2001) Single nucleotide polymorphisms in the methylenetetrahydrofolate reductase gene are common in US Caucasian and Hispanic American populations. |
3. |
Födinger M et al. (1997) Mutation (677 C to T) in the methylenetetrahydrofolate reductase gene aggravates hyperhomocysteinemia in hemodialysis patients. |
4. |
Orphanet article Orphanet ID 123529 |
5. |
NCBI article NCBI 4524 |
6. |
OMIM.ORG article Omim 607093 |
7. |
Wikipedia article Wikipedia EN (Methylenetetrahydrofolate_reductase) |