Increased risk for deep vein thrombosis in persons with coagulation deficiency, risk factors such as oral contraceptives, smoking, positive family history for dementia or Alzheimer disease.
Methylene-Tetrahydrofolate-Reductase-gene-mutation - MTHFR
Clinical Features
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.
Genetic Information
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.
Prevalence
Mutation 677C>T and Mutation 1298A>C:
Heterozygotes: ca. 1 : 2,5
Homozygotes: ca. 1 : 6
Diagnostic
Indication
Method
Allele specific PCR
Sample Requirement
2 - 4 ml of EDTA-blood
Duration
approx. 2 weeks