High altitude pulmonary oedema (HAPE) is a severe form of altitude illness that may develop in individuals on rapid ascent to altitudes above 2500 m.¹ The disease is characterised by hypoxia induced pulmonary vasoconstriction caused by endothelial dysfunction and intravascular fluid retention.^2,3 While some families and individuals are at risk, those with a long ancestry at high altitude have a lower risk. Moreover, individuals who have had HAPE are at a greater risk of repeat events. Such data support a strong genetic component to HAPE susceptibility, perhaps associated with a founder effect. It is likely that long term exposure to high altitude provides a natural positive adaptive pressure to alleles that prevent the illness. We hypothesise that allelic variants at the same locus in a gene are involved in adaptation and HAPE.

We therefore investigated the Glu298Asp and 4b/4a polymorphisms of the endothelial nitric oxide synthase gene (eNOS) and −344T/C, intron-2 conversion and Lys173Arg polymorphisms of the aldosterone synthase gene (CYP11B2) in 59 patients with HAPE who developed the disease at 3400 m, …