SOD2 V16A is associated with clinical markers of endothelial dysfunction and increases extracellular hydrogen peroxide and mitochondrial superoxide production. (A) Tricuspid regurgitant velocity (TRV), (B) systolic blood pressure, (C) right ventricular area at systole, (D) 6-minute walk distance of Walk-PhaSST cohort by SOD2 16th amino acid genotype, and (E) interaction between lactate dehydrogenase and TRV by SOD2 16th amino acid genotype P for interaction of LDH and genotype <.001. (F) Plasmid schematic of SOD2 lentiviral and (G) protein expression between 2 SOD2 variants. (H) Extracellular hydrogen peroxide and (I) mitochondrial reactive oxygen species produced by each SOD2 variant with and without antimycin A. Results in panels A-E are in mean with standard error of the mean. In panels A-D, β is a measure of change in outcome by each minor allele (additive model) and P values represent the test for trend. In panel E, interaction between SOD genotype and LDH was tested in a linear regression analysis. P values test the correlation between TRV and LDH in each SOD genotype. Results in panels G-I are given in mean ± standard deviation. AA represents patients with the alanine variant of SOD2, AG represents patients with the alanine/valine variant, and GG represents patients with the valine variant. LDH, lactate dehydrogenase.