Performance at altitude and angiotensin I-converting enzyme genotype

The "insertion" (I) rather than "deletion" (D) variant of the human angiotensin-converting enzyme (ACE) gene is associated with both lower tissue ACE activity and elite performance at high altitude. We examined whether the onset of acute mountain sickness (AMS), and further performance on reaching the summit of Mt. Blanc are influenced by the ACE I/D polymorphism. Two hundred and eighty-four climbers (235 males, [37.0 (11.0 years], (86 DD, 142 ID, 56 II)) had assessment of their AMS status upon arrival to the Gouter hut (3,807 m) on day 1, and again on day 2 after an attempted ascent to the summit of Mt. Blanc (4,807 m). Success in reaching the summit was genotype dependent (87.7% of DD, 94.9% of ID and 100% of II individuals; P=0.048); I allele frequency for those reaching the summit was 0.47 compared to 0.21 for those who did not (P=0.01). The onset of AMS on day 1 appeared to be dependent on genotype (P=0.003), but with those heterozygous being less affected. ACE genotype was not associated either with AMS onset or severity on day 2. Thus, ACE I/D genotype is associated with successful high altitude ascent in this prospective study-an association not explicable by genotype-dependence of AMS onset or severity. Values are given as mean (SD) unless otherwise stated.