Homocystine is the Etiologic Factor in Occlusive Vascular Diseases
Homocystine (d) is the correct answer as it is a well-established etiologic factor in occlusive vascular diseases. Multiple guidelines identify hyperhomocysteinemia as an independent risk factor for various types of vascular occlusive disorders.
Mechanism and Evidence
Hyperhomocysteinemia (elevated blood levels of homocystine) has been recognized as an independent risk factor for premature vascular occlusion 1. The American Society of Human Genetics and American College of Medical Genetics have established that elevated total plasma homocysteine (tHcy) levels greater than 15 μM constitute hyperhomocysteinemia, with even levels between 10-15 μM potentially increasing risk 1.
The American Heart Association guidelines specifically identify homocystinuria as a cause of both arterial and venous occlusion 1. Three enzyme deficiencies can lead to homocystinuria:
- Cystathionine β-synthetase deficiency
- Homocysteine methyltransferase deficiency
- Methylenetetrahydrofolate reductase (MTHFR) deficiency
Clinical Significance
Hyperhomocysteinemia has been associated with:
- Cerebral arterial and venous thrombosis in children and adults 1
- Coronary artery disease 1
- Peripheral arterial occlusive disease 1
- Retinal vein occlusions 1
Research evidence shows that hyperhomocysteinemia is present in:
- 42% of patients with cerebrovascular disease
- 28% with peripheral vascular disease
- 30% with coronary artery disease 2
The Physician's Health Study found that an increase in homocysteine concentration of just 1.7 μmol/L above normal values was associated with a threefold higher risk for myocardial infarction 2.
Comparison with Other Options
None of the other amino acids listed in the question options have been identified as independent risk factors for occlusive vascular disease:
- Arginine (a): Actually has potential vasodilatory effects through nitric oxide pathways
- Glutamine (b): No established role in vascular occlusive disease
- Methionine (c): While it is a precursor to homocysteine in metabolism, it's not directly implicated as an independent risk factor
- Xanthine (e): Associated with gout but not directly with occlusive vascular disease
Clinical Applications
Identifying hyperhomocysteinemia is important in patients with:
- Premature vascular disease
- Retinal vascular occlusions
- Unexplained arterial or venous thrombosis
- Family history of early cardiovascular events
Treatment approaches for hyperhomocysteinemia typically involve supplementation with B vitamins (folate, B6, B12) which serve as cofactors in homocysteine metabolism 1, 2.
Important Considerations
- Sample collection for homocysteine measurement requires precise handling, including immediate separation and freezing of plasma 1
- The etiologies of hyperhomocysteinemia are complex, involving both genetic and environmental factors 1
- Inappropriate supplementation of cofactors can be harmful, so identifying the specific cause of hyperhomocysteinemia is important prior to treatment 1
In conclusion, among the options presented, homocystine (d) is the only amino acid that has been definitively established as an etiologic factor in occlusive vascular diseases based on extensive clinical evidence and guideline recommendations.