Plasma levels of extracellular superoxide dismutase in an Australian population - Genetic contribution to normal variation and correlations with plasma nitric oxide and apolipoprotein A-I levels

Extracellular superoxide dismutase (EC-SOD) is a major superoxide scavenger and may be important to normal vascular function and cardiovascular health . We analyzed family data from 610 healthy Australians to detect and quanti fy the effects of genes on normal variation in plasma levels of EC-SOD and to test for pleiotropy with plasma nitric oxide (NO) and apolipoprotein A-I (apoA-I). Using maximum-likelihood-based variance decomposition methods, w e determined that sex, age, and plasma levels of HDL cholesterol, apoA-I, a nd creatinine accounted for 38.6% of the variance in plasma EC-SOD levels a nd that additive genes accounted for 35% (P<0.00002). Multivariate analyses of plasma levels of EC-SOD, NOx (a measure of basal NO production), and ap oA-I detected significant genetic correlations, indicating pleiotropy betwe en EC-SOD and apoA-I (genetic correlation [rho(G)]=-0.45) and between NOx a nd apoA-I (rho(G)=0.58) but not between EC-SOD and NOx. Genes shared by EC- SOD and apoA-I account for 20% of the genetic variance and, respectively, 7 % and 9% of the phenotypic variance in both traits. Shared genes also accou nt for >33% of the genetic variance and 5% and 15% of the respective phenot ypic variance in NOx and apoA-I. In healthy individuals, over a third of th e variance in EC-SOD plasma levels is due to the additive effects of genes. Some genes influence EC-SOD and apoA-I levels. The same is true of NOx and apoA-I but not of EC-SOD and NOx. These patterns of pleiotropy can guide s ubsequent attempts to identify the genes and physiological mechanisms under lying them.