Genetics of homocysteine metabolism and associated disorders.
Level 5 - mechanism / opinion, no new human data
Narrative review without systematic search or meta-analytic methodology
PubMed 19967264 · doi:10.1590/s0100-879x2009007500021
What was done
The authors synthesized narrative literature on homocysteine biochemistry (remethylation and transsulfuration pathways), genetic polymorphisms encoding relevant metabolic enzymes (focusing on methylenetetrahydrofolate reductase [MTHFR] variants 677C>T and 1298A>C), associated clinical disorders, and the clinical utility of folic acid supplementation and fortification.
What was found
The review reports that hyperhomocysteinemia affects approximately 5% of the general population. It notes associations between elevated homocysteine and multiple conditions, including vascular and neurodegenerative diseases, autoimmune disorders, birth defects, diabetes, renal disease, osteoporosis, neuropsychiatric disorders, and cancer. The authors also report that folic acid fortification and supplementation associate with reduced prevalence of congenital anomalies and declining stroke mortality. No effect sizes, odds ratios, or quantitative meta-analytic data are provided in the abstract.
Why it matters
It provides an overview linking one-carbon metabolism defects—principally MTHFR variants—to widespread chronic and developmental pathologies, highlighting public health strategies like folic acid fortification.
Limits
This is a narrative review with no systematic search methodology, risk-of-bias evaluation, or pooled statistical analyses reported. The abstract provides no specific quantitative risk metrics or sample sizes.
Cited by
- contradicts Homocysteine is normally metabolized through the urea cycle to succinate by the enzyme methylenetetrahydrofolate reductase (MTHFR).