Second, increased PNP activity (largely on its own, but also in concert with ADA and GDA) would result in overproduction and accumulation of vasculotoxic hypoxanthine and xanthine [22] that cause oxidative stress‐induced endothelial dysfunction [19, 22], have pro‐inflammatory effects, and are involved in blood cell aggregation, ischemia/reperfusion injury [61] and chronic pain. This evidence concerns the gene ADA and endothelial dysfunction.