Gene polymorphisms and high-altitude pulmonary edema susceptibility: a 2011 update.

High-altitude pulmonary edema (HAPE) is a severe disease caused by high-altitude hypoxia. Since some individuals are more susceptible to high altitude than others, the incidence is variable and cannot be predicted. Furthermore, multiple genes can contribute to the occurrence of HAPE, making it even more difficult to predict. The genes associated with HAPE include those in the renin-angiotensin-aldosterone system pathway, the nitric oxide pathway and the hypoxia-inducible factor pathway. Other genes associated with HAPE include tyrosine hydroxylase (TH), vascular endothelial growth factor (VEGF), pulmonary surfactant proteins and β(2)-adrenergic receptor. The association of the polymorphisms of these genes with HAPE susceptibility has previously been investigated. Among the genes evaluated, polymorphisms of NOS3, ACE, CYP11B2, Hsp70 and endothelin-1 and pulmonary surfactant proteins A1 and A2 were shown to be associated with HAPE incidence, while associations between TH, VEGF and HAPE remain to be fully elucidated. Novel technological approaches, including genome-wide association studies and next-generation sequencing, are currently being used to identify new HAPE susceptibility genes. The goal of this review article is to summarize the current literature and to define the outstanding areas of research that need to be explored to advance our ability to predict when HAPE will occur.