Clinical relevance
Hyperhomocysteinemia has emerged as a riskfactor for coronary artery
disease (1).
The metabolism of homocysteine occurs through two pathways. Genetic
defects in genes of the involved enzymes are associated with hyperhomocysteinemia.
One of the pathways contains the enzyme methylenetetrahydrofolate
reductase (MTHFR), which catalyses the remethylation of homocysteine
to methionine.
A common polymorphism in the MTHFR gene correlates with the characteristics
of a thermolabile MTHFR protein. The heat-sensitive variant of the
enzyme has only 50% of the activity of the normal enzyme (2). The
mutation responsible for this form is a C (cytosin) to T (thymidine)
substitution at nucleotide 677 of the coding sequence which converts
an alanine to a valine residue (3).
The plasma homocysteine levels in individuals homozygous for this
mutation were significantly higher than those of other individuals
(3).
The MTHFR-C677T polymorphism is very common. About 40% of the population
are homozygous for the wildtype C677, 45% are heterozyous for both
alleles C677 and T677 and about 15% are homozygous carrier for the
T677 mutated allele (4).
Several investigations have shown that the homozygous mutated genotype
is a independent risk factor for coronary artery disease (3, 5-7).
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