Genetics of pulmonary hypertension and high-altitude pulmonary edema
Christina A. Eichstaedt, Nicola Benjamin, Ekkehard Grünig
Abstract
Heritable pulmonary arterial hypertension (PAH) is an autosomal dominantly inherited disease caused by mutations in the bone morphogenetic protein receptor 2 ( BMPR2) gene and/or genes of its signaling pathway in ~85% of patients. A genetic predisposition to high-altitude pulmonary edema (HAPE) has long been suspected because of familial HAPE cases, but very few possibly disease-causing mutations have been identified to date. This minireview provides an overview of genetic analyses investigating common polymorphisms in HAPE-susceptible patients and the directed identification of disease-causing mutations in PAH patients. Increased pulmonary artery pressure is highlighted as an overlapping clinical feature of the two diseases. Moreover, studies showing increased pulmonary artery pressures in HAPE-susceptible patients during exercise or hypoxia as well as in healthy BMPR2 mutation carriers are illustrated. Finally, high-altitude pulmonary hypertension is introduced and future research perspectives outlined.