ABSTRACT
The topic of genetics in relation to high altitude is a fast-moving area and justifies its own chapter in this new edition. In the past many people commented on the superior exercise ability of highlanders such as Tibetans and Andeans but, of course, only recently has it become possible to determine the genetic basis if this exists. One of the first areas of research was the effects of polymorphism of the ACE gene. These variants are believed to influence athletic ability although their importance at high altitude is still uncertain. A major advance was the discovery of hypoxiainducible factors which are now known to play major roles in the expression of genes related to hypoxia. At high altitude they alter erythropoiesis, the ventilatory response to hypoxia and hypoxic pulmonary vasoconstriction among other functions. An exciting advance has been the discovery of genetic changes in Tibetans, being reported in no less than seven independent publications in 2010. Research in this area is moving rapidly but it is clear that a major gene is EPAS1 which codes for HIF-2α and therefore has a large variety of physiological effects. Studies of genetic changes in other high altitude populations, such as those in the South American Andes and
Ethiopia, are ongoing. Another important area is the role of genetic factors in high altitude diseases. Different susceptibilities of individuals, families and populations suggest that genetic factors play a role and a large number of candidate genes are under investigation. Finally, the remarkable phenotype differences between Tibetans and Andeans are reviewed. The fact that these two groups of highlanders who have both adapted so successfully to high altitude have very different physical make-ups is tantalizing and is provoking much research.
