No association between high-altitude tolerance and the ACE I/D gene polymorphism

The absence (deletion allele [D]) of a 287 base-pair fragment in the ACE gene is associated with higher ACE tissue activity than its presence (insertion allele [I]) and, as such, may enhance vasoconstriction and fluid retention through increased levels of angiotensin II and aldosterone. Because fluid retention is found in acute mountain sickness (AMS) and exaggerated pulmonary hypertension is essential in the pathophysiology of high-altitude pulmonary edema (HAPE), we hypothesized that the DD genotype is associated with increased susceptibility to these illnesses.

ACE genotype was thus determined in 83 mountaineers staying over night at 4559 m and related to AMS symptoms. Genotype was similarly determined in 76 mountaineers who had participated in previous studies at 4559 m; 38 of the latter group had a history of HAPE, and 25 had developed HAPE again during these studies.

The allele frequency was in Hardy-Weinberg equilibrium in both investigations. Neither the history nor the observed episodes of HAPE nor the prevalence of AMS defined as an AMS-C score >/= 0.70 (environmental symptom questionnaire) in the first study or in both studies taken together were significantly different between the genotypes DD, ID, and II.

We conclude that I/D-ACE gene polymorphism has no important effect on susceptibility to AMS or HAPE.