Homocysteinemia, ischemic heart disease, and the carrier state for homocystinuria.
Precocious atherosclerosis occurs in homocystinuria due to cystathionine beta-synthase deficiency and there is evidence that homocysteine may produce endothelial damage. Mild homocysteinemia has been reported in heterozygotes after methionine loads and it has been suggested that they could have an increased risk of atherogenesis. We measured plasma amino acids before and after a methionine load (100 mg per kg) in 17 obligatory heterozygotes, in 20 men under 50 yr with established ischemic heart disease, and in matched controls, to determine whether methionine loading allows identification of heterozygotes, and whether there is an altered rate of methionine metabolism in patients with premature coronary artery disease. The obligate heterozygotes had higher mean plasma concentrations of methionine and total homocysteine at 4, 8 and 12 hours after the load than their controls, and lower concentrations of total cysteine and taurine in fasting and all post load samples; however, there was considerable overlap of measurements in heterozygotes and their controls even when differential weightings were applied. There were no differences in mean plasma concentrations of methionine, total homocysteine or total cysteine between the patients with ischemic heart disease and their controls at any measurement point. However, two patients with premature coronary artery disease, identical twins, had persistent elevation of total plasma homocysteine and an exaggerated homocysteine response to methionine. Oral folate restored homocysteine concentrations before and after methionine to normal.(ABSTRACT TRUNCATED AT 250 WORDS)
D000328:Adult; D000603:Amino Acids, Sulfur / Q000097:blood; D000613:Aminobutyrates / Q000097:blood; D003327:Coronary Disease / Q000097:blood / Q000235:genetics*; D004200:Diseases in Twins; D005260:Female; D006579:Heterozygote; D006710:Homocysteine / Q000097:blood*; D006712:Homocystinuria / Q000097:blood / Q000235:genetics*; D006801:Humans; D008297:Male; D008715:Methionine / Q000378:metabolism; D008875:Middle Aged; D009203:Myocardial Infarction / Q000235:genetics; D011247:Pregnancy; D014430:Twins, Monozygotic
D000603:Amino Acids, Sulfur; D000613:Aminobutyrates; D006710:Homocysteine; C012223:alpha-aminobutyric acid; D008715:Methionine