Relationship Between Homocysteine and Superoxide Dismutase in Homocystinuria

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Abstract
—A modest homocysteine elevation is associated with an increased cardiovascular risk. Marked circulating homocysteine elevations occur in homocystinuria due to cystathionine β-synthase (CβS) deficiency, a disorder associated with a greatly enhanced cardiovascular risk. Lowering homocysteine levels reduces this risk significantly. Because homocysteine-induced oxidative damage may contribute to vascular changes and extracellular superoxide dismutase (EC-SOD) is an important antioxidant in vascular tissue, we assessed EC-SOD and homocysteine in patients with homocystinuria. We measured circulating EC-SOD, total homocysteine (free plus bound), and methionine levels during the treatment of 21 patients with homocystinuria, 18 due to CβS deficiency, aged 8 to 59 years, and 3 with remethylating defects. We measured total homocysteine by immunoassay, EC-SOD by ELISA, and methionine by amino acid analysis and assessed interindividual and intraindividual relationships. There was a significant, positive relationship between EC-SOD and total homocysteine. For the interindividual assessment, levels were highly correlated, r =0.746, N=21, P r =0.607, N=62, P r =0.148, n=39, P =0.368). The positive relationship between circulating EC-SOD and homocysteine could represent a protective antioxidant response to homocysteine-induced oxidative damage and contribute to reducing cardiovascular risk in homocystinuric patients. EC-SOD levels may be relevant to the pathogenesis of vascular disease in other patient groups.