Aktuelle Neurologie 2004; 31 - P518a
DOI: 10.1055/s-2004-833380

Genetics and vitamins of homocysteine metabolism: impact on neurodegenerative, cerebrovascular and neurooncological disorders

M Linnebank 1, H Kölsch 1, U Schlegel 1, T Klockgether 1, U Wüllner 1
  • 1(Bonn)

Methionin and homocysteine (Hcy) metabolism is of particular importance for CNS myelination, glutathione production, collagen cross-linking and nucleic acid synthesis. Dependency on several vitamins like riboflavin, pyridoxalphosphate, folate and cobalamin (B2, 6, 9, 12) and the presence of a number of functional polymorphisms account for the high interindividual variability of Hcy metabolism kinetics. The Hcy metabolism thus represents a promising candidate for the search of individual dispositions to neurodegenerative, vascular and oncological disorders.

We review the biochemical and medical basics of Hcy metabolism and its vitamins with particular emphasis on diagnosis and therapy of the clinically most relevant metabolic impairments.

In addition, we summarize the results of our current studies showing associations of Hcy genetics with various neurological conditions (p-values or Chi2 and Kaplan-Meier analysis):

The methylenetetrahydrofolate reductase (MTHFR) polymorphism c.1298A>C (E429A) influenced the age of onset in patients with Alzheimer's disease (p=0.029), Parkinson's disease (p=0.007) and multiple system atrophy (p=0.010). The MTHFR polymorphism c.677C>T (A222V) was a minor factor of vulnerability for stroke in patients younger than 60 years (p=0.043) and conferred a risk of CNS demyelination in patients with adrenomyeloneuropathy (p=0.032). The methionine synthase polymorphism c.2756A>G (D919G) had a protective function against the incidence of primary central nervous system lymphoma (p=0.005). Moreover, we found that this polymorphism, which had been reported to protect against additional cancer enteties, was associated with longevity free of neurological, psychiatric and internal diseases (p=0.005). Our data underpin the necessity for further systematic analyses of the influence of the Hcy metabolism on the incidence or course of neurodegenerative, cerebrovascular and oncological disorders.