Relationship between total plasma homocysteine, polymorphisms of homocysteine metabolism related enzymes, risk factors and coronary artery disease inthe Australian hospital-based population

Modest elevations of circulating homocysteine are common in patients with v ascular disease. We explored interrelations between total plasma homocystei ne levels and mutations in genes for three key enzymes in methionine-homocy steine metabolism. Methyltetrahydrofolate reductase (MTHFR) 677C --> T, cys tathionine beta,synthase (CBS) 68-bp insertion at exon 8, and methionine sy nthase (MS) 2756A --> G were typed in 685 Australian caucasian patients age d less than or equal to 65 years with and without angiographically document ed coronary artery disease (CAD). We also assessed associations between hom ocysteine levels and extracellular superoxide dismutase (EC-SOD) and other CAD risk factors. There were significant correlations between plasma total homocysteine, and EC-SOD (r = 0.170, p = 0.001 for men; r = 0.241, p = 0.00 3 for women) and LDL (r = 0.153, p = 0.001 for men; r = 0.132, p = 0.081 fo r women). Levels were also significantly higher among patients with unstabl e angina (15.30 +/- 0.44 mu mol/l for men, 14.44 +/- 0.74 mu mol/l for wome n) than those without angina (13.98 +/- 0.38 mu mol/l for men, 13.41 +/- 0. 98 mu mol/l for women) or with stable angina (14.00 +/- 0.37 mu mol/l for m en, 12.88 +/- 0.71 mu mol/l for women). There were no significant associati ons between the levels and the presence or severity of CAD. The mutant MTHF R homozygotes tended to have higher levels and those with the MS and CBS mu tations tended to have lower levels. We conclude that there is a significan t correlation between plasma homocysteine levels and EC-SOD suggesting that elevated homocysteine may exert oxidative stress and that levels are assoc iated with unstable angina, but not the occurrence or extent of coronary st enosis. The contributions to total plasma homocysteine levels of the common mutations of genes coding for the enzymes controlling homocysteine metabol ism are modest. (C) 1999 Elsevier Science ireland Ltd, All rights reserved.