Angiotensin-converting enzyme and genetics at high altitude

As part of the renin-angiotensin system (RAS), angiotensin-converting enzyme (ACE) plays a key role in circulatory homeostasis. ACE degrades vasodilator kinins and generates angiotensin II. A polymorphism in intron 16 of the human ACE gene has been identified in which the presence (insertion, I allele) rather than the absence (deletion, D allele) of a 287 bp fragment is associated with lower serum and tissue ACE activity. The I allele has been associated with some aspects of endurance performance, being found with excess frequency in elite distance runners, rowers, and other elite athletes. Mountaineers also demonstrate an allele skew with a significant excess of the I allele and II genotype in elite, male, British mountaineers who have ascended beyond 7000 m without the use of supplemental oxygen. This review evaluates the evidence for and against an association of the I allele with human endurance, and performance at high altitude. We conclude that the I allele does confer an advantage, most likely mediated via improved muscle efficiency with secondary benefits in terms of conservation of non-fat mass.