Two variants of extracellular-superoxide dismutase: Relationship to cardiovascular risk factors in an unselected middle-aged population

Objective. Description of the distribution of plasma levels of two Variants of extracellular-superoxide dismutase (EC-SOD) and their relationship to cardiovascular risk factors in the general population. Design. A cross-sectional study. Setting, Norrbotten and Vasterbotten counties in northern Sweden. Subjects, Four thousand, nine hundred 25-74-year-old randomly selected subjects. Main outcome measures. Plasma levels of EC-SOD. Genotyping by an allele-specific PCR method. Results. Plasma EC-SOD levels showed a distinct bimodal distribution with the smaller group (3.8%) having a variant of the enzyme with about eight-fold-higher plasma levels. Genotyping was performed in 65 individuals with the high-level variant. All but one were found to carry the same mutation, Arg213Gly, affecting the heparin-binding domain of EC-SOD. Subjects with the high-level Variant of EC-SOD had modestly higher body mass index and higher levels of serum cholesterol, serum triglycerides and plasma fibrinogen than those with the common EC-SOD phenotype. Within the population with common EC-SOD, the plasma levels were lower in men than in women and increased with age. Low levels of common phenotype EC-SOD were associated with smoking, high plasma levels of fibrinogen and low activity of tissue plasminogen activator in both univariate and multivariate analyses. Obesity and total serum cholesterol were associated with high common phenotype EC-SOD levels. Conclusions. A high-level variant of EC-SOD caused by one and the same mutation and with low tissue binding and high plasma levels is present in approximately four per cent of an unselected middle-aged population in northern Sweden. Plasma levels of EC-SOD may be modulated by lifestyle factors such as smoking and show a complex covariation with many of the conventional cardiovascular risk factors.