Methylene-Tetrahydrofolate-Reductase-gene-mutation - MTHFR

Klinische Symptomatik

The enzyme methylenetetrahydrofolate reductase (MTHFR) participates in the conversion from homocysteine to methionine. A genetically determined deficiency of MTHFR results in reduced enzymatic activity consequently leading to increased homocysteine levels. Increased homocysteine levels are regarded as risk factor for atherosclerotic lesions and venous thromboembolisms. A possible association of increased homocysteine and the development of dementia or Alzheimers disease has also been described. In pregnant women, increased homocysteine levels are associated with a higher probability for neural tube defects. Women at risk should be recommended the daily intake of 5 mg folate prior to conception up the end of the first trimester. A control of serum homocysteine levels and corresponding folate intake is also recommended for other persons with genetic predisposition to hyperhomocysteinemia.

Genetik

The MTHFR (methylenetetrahydrofolate reductase) gene is located on chromosome 1 (1p36.3). Genetic alterations of the MTHFR gene caused by two different SNPs (single nucleotide polymorphism; 677C>T and 1298A>C) result in a reduced enzyme activity leading to increased homocysteine. 40% of the normal population are heterozygous carriers of the SNP at position 677, i.e. they carry a T at position 677 on one of their two alleles. In these persons, homocysteine levels usually are normal, but may be slightly increased. 16% of the normal population are homozygous carriers of the SNP at position 677, i.e. they carry a T at position 677 on both their alleles. C>T. Homocysteine levels are significantly increased. Concomitant homozygosity or heterozygosity for a second SNP at position 1298 may favor a further increase of homocysteine levels in these persons. Especially, the presence of additional risk factors (e.g. Factor V Leiden mutation) may result in an increased risk for venous thromboses.

Häufigkeit

Mutation 677C>T and Mutation 1298A>C:
Heterozygotes:  ca. 1 : 2,5
Homozygotes:   ca. 1 : 6

 

Diagnostik