title: Relationship between homocysteine and superoxide dismutase in homocystinuria: possible relevance to cardiovascular risk.
abstract: A modest homocysteine elevation is associated with an increased cardiovascular risk. Marked circulating homocysteine elevations occur in homocystinuria due to cystathionine beta-synthase (CbetaS) 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 CbetaS 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<0.0001. This relationship was maintained after taking into account intraindividual patient variation (r=0.607, N=62, P<0.0001). In 2 newly diagnosed CbetaS-deficient patients, treatment that lowered the markedly elevated pretreatment homocysteine level (from 337 to 72 and from 298 to 50 micromol/L) reduced the associated elevated EC-SOD in each by 50%. EC-SOD and methionine levels were unrelated (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.
authors.affiliation: Department of Cardiovascular Medicine, Prince of Wales Hospital, Sydney, Australia. d.wilcken@unsw.edu.au
authors.forename: D E
authors.initials: DE
authors.lastname: Wilcken
authors.forename: X L
authors.initials: XL
authors.lastname: Wang
authors.forename: T
authors.initials: T
authors.lastname: Adachi
authors.forename: H
authors.initials: H
authors.lastname: Hara
authors.forename: N
authors.initials: N
authors.lastname: Duarte
authors.forename: K
authors.initials: K
authors.lastname: Green
authors.forename: B
authors.initials: B
authors.lastname: Wilcken
mesh_terms: D000293:Adolescent; D000328:Adult; D002318:Cardiovascular Diseases / Q000209:etiology*; D002648:Child; D003541:Cystathionine beta-Synthase / Q000172:deficiency; D005260:Female; D006710:Homocysteine / Q000097:blood*; D006712:Homocystinuria / Q000097:blood* / Q000201:enzymology; D006801:Humans; D008297:Male; D008715:Methionine / Q000097:blood; D008875:Middle Aged; D018384:Oxidative Stress; D012307:Risk Factors; D013482:Superoxide Dismutase / Q000097:blood*
chemical_list: D006710:Homocysteine; D008715:Methionine; D013482:Superoxide Dismutase; D003541:Cystathionine beta-Synthase