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Plasma homocysteine and lipoprotein profile in patients with peripheral arterial occlusive disease
F Rassoul1, V Richter, C Janke
1Department of Clinical Chemistry and Pathobiochemistry, University Leipzig/Working Group Health Promotion and Prevention of Atherosclerosis e.V., Germany.
Insights
Moderate hyperhomocysteinemia (HCy) is linked to peripheral arterial occlusive disease (PAOD). Elevated homocysteine levels and altered lipoprotein profiles are common in PAOD patients, suggesting HCy as a significant risk factor.
Area of Science:
- Cardiovascular Science
- Metabolic Disorders
- Genetics
Background:
- Moderate hyperhomocysteinemia (HCy) is an established independent risk factor for atherosclerosis.
- Peripheral arterial occlusive disease (PAOD) is a manifestation of atherosclerosis, impacting circulation in the limbs.
Purpose of the Study:
- To investigate the association between homocysteine levels, lipoprotein profiles, and PAOD in male patients.
- To determine the prevalence of hyperhomocysteinemia and its correlation with specific genetic mutations in PAOD patients.
Main Methods:
- Case-control study involving 85 male PAOD patients and 51 age-matched male controls.
- Analysis of serum lipid profiles, including cholesterol, triglycerides, HDL, LDL, and apolipoproteins (apo B, apo A-I).
- Measurement of serum homocysteine, folic acid, and vitamins B12 using high-pressure liquid chromatography; MTHFR gene mutation analysis (677 C --> T).
Main Results:
- PAOD patients exhibited significantly higher mean homocysteine concentrations (p<0.001) compared to controls.
- Hyperhomocysteinemia (>16 micromol/L) prevalence was 45% in PAOD patients versus 8% in controls.
- Reduced HDL cholesterol, HDL3 cholesterol, Apo A-I, Lp A-I, and elevated triglycerides were observed in PAOD patients; negative correlations between homocysteine and vitamin B12/folic acid levels.
Conclusions:
- Elevated plasma homocysteine is strongly associated with PAOD.
- Specific genetic mutations in the methylenetetrahydrofolate reductase (MTHFR) gene (677 C --> T) are linked to elevated homocysteine in PAOD patients.
- The findings support hyperhomocysteinemia as a critical risk factor in the pathogenesis of peripheral arterial occlusive disease.
Abstract:
Several studies have identified moderate hyperhomocysteinemia (HCy) as an independent risk factor for atherosclerosis. The purpose of this case control study was to determine lipoprotein profile and homocysteine concentration in serum of 85 male patients with peripheral arterial occlusive disease (PAOD) and in 51 normolipidemic age-matched male controls. Cholesterol, triglycerides, and high-density lipoprotein (HDL) cholesterol as well as subfractions HDL2 and HDL3 cholesterol, low-density lipoprotein (LDL) cholesterol, apo B, apo A-I, and lipoprotein particles LpA-I and LpA-I:A-II were measured in serum. Homocysteine, folic acid, and vitamins B6 and B12 were determined with the help of high-pressure liquid chromatography. The 677 C --> T mutation in the methylenetetrahydrofolate reductase (MTHFR) gene was analyzed in PAOD patients. Patients with peripheral arterial occlusive disease showed a significantly higher mean concentration of homocysteine than control subjects (p<0.001). There was a negative correlation between the levels of homocysteine and vitamin B12 as well as folic acid (for vitamin B12: r=-0.40 and for folic acid: r=-0.38). The prevalence of hyperhomocysteinemia (Hcy >16 micromol/L) in the patients was 45% in contrast to 8% in controls. HDL cholesterol, HDL3 cholesterol, Apo A-I, and Lp A-I were significantly reduced in patients and triglycerides were elevated. The elevated plasma homocysteine concentration is frequently seen in homozygous carriers of a point mutation (677 C --> T) in the methylenetetrahydrofolate reductase gene, as the product of this gene is an enzyme, participating in homocysteine remethylation. The homozygous state for the 677 C --> T mutation was found in 13.3% of PAOD patients.