Genetisk betinget reduktion i antioxidativ beskyttelse og öget risiko for iskaemisk hjertesygdom - sekundaerpublikation
Österbroundersögelsen
Sammanfattning
Introduction: Extracellular superoxide dismutase (EC-SOD) is an anti-oxidative enzyme found in high concentrations in the arterial wall. 2-3% of the population carry an R213G substitution, which increases plasma concentration 10-fold. This may reduce arterial wall EC-SOD concentrations, increase LDL oxidation, and therefore accelerate atherogenesis. We tested the hypotheses that EC-SOD-R213G predisposes to ischemic heart disease (IHD) and that EC-SOD-R213G genotyping offers predictive ability with respect to IHD beyond that offered by measurements of plasma EC-SOD. Materials and methods: The primary hypothesis was tested in a prospective, population-based study of 9,188 participants from the Copenhagen City Heart Study with a total of 956 IHD events during 23 years of follow-up and retested in two case-control studies in which 943 IHD patients and 617 patients with ischemic cerebrovascular disease (ICVD) were compared with 7,992 IHD/ICVD-free controls from the Copenhagen City Heart Study. The secondary hypothesis was tested using a nested IHD case-control study within the Copenhagen City Heart Study (n = 956 + 956). Results: The age and gender-adjusted relative risk for IHD in heterozygotes (n = 221, 2.4%) versus non-carriers (n = 8,965, 97.6%) was 1.5 (95% CI: 1.1-2.1). Re-testing confirmed this: the age and gender-adjusted odds ratios for IHD were 1.4 (1.0-2.0) and for ICVD 1.7 (1.1-2.7). Additional adjustment for plasma EC-SOD produced an odds ratio of 9.2 (1.2-72). Discussion: Heterozygosity for EC-SOD-R213G is associated with increased IHD risk. Genotyping offers predictive ability with respect to IHD beyond that offered by plasma EC-SOD.