A candidate genetic risk factor for vascular disease: a common mutation in methylenetetrahydrofolate reductase.
Level 4 - case-series / case-control
Cross-sectional genetic association and in vitro functional study without longitudinal clinical outcomes.
PubMed 7647779 · doi:10.1038/ng0595-111
What was done
Investigators identified a mutation altering a conserved amino acid in the 5,10-methylenetetrahydrofolate reductase (MTHFR) gene and determined its frequency across unselected chromosomes. The functional impact was evaluated by measuring MTHFR enzymatic activity and thermolability in lymphocyte extracts from heterozygous and homozygous individuals and by in vitro expression of mutagenized cDNA. Plasma homocysteine concentrations were compared across genotypes.
What was found
The MTHFR mutation was present at an allele frequency of approximately 38% in unselected chromosomes. In both heterozygous and homozygous states, the mutation correlated with reduced enzyme activity and increased thermolability in lymphocyte extracts, consistent with results from in vitro cDNA expression. Homozygous individuals had significantly elevated plasma homocysteine levels. Exact participant counts, quantitative enzyme activity levels, homocysteine values, and p-values were not reported in the abstract.
Why it matters
This study identifies the common MTHFR genetic mutation responsible for enzyme thermolability and elevated plasma homocysteine, establishing a molecular mechanism for a widespread candidate genetic risk factor in vascular disease.
Limits
The abstract does not provide sample sizes, participant demographics, quantitative biochemical values, effect sizes, or confidence intervals. Clinical vascular outcomes and disease incidence were not directly measured.
Cited by
- context A homozygous MTHFR polymorphism reduces the MTHFR enzyme's efficiency to roughly 10% to 20% of normal function.