Angiotensin-converting enzyme genotype and successful ascent to extreme high altitude.
Interindividual variation in acclimatization to altitude suggests a genetic component, and several candidate genes have been proposed. One such candidate is a polymorphism in the angiotensin converting enzyme (ACE) gene, where the insertion (I-allele), rather than the deletion (D-allele), of a 287 base pair sequence has been associated with lower circulating and tissue ACE activity and has a greater than normal frequency among elite endurance athletes and, in a single study, among elite high altitude mountaineers. We tested the hypothesis that the I-allele is associated with successful ascent to the extreme high altitude of 8000 m. 141 mountaineers who had participated in expeditions attempting to climb an 8000-m peak completed a questionnaire and provided a buccal swab for ACE I/D genotyping. ACE genotype was determined in 139 mountaineers. ACE genotype distribution differed significantly between those who had successfully climbed beyond 8000 m and those who had not (p = 0.003), with a relative overrepresentation of the I-allele among the successful group (0.55 vs. 0.36 in successful vs. unsuccessful, respectively). The I-allele was associated with increased maximum altitudes achieved: 8079 +/- 947 m for DDs, 8107 +/- 653 m for IDs, and 8559 +/- 565 m for IIs (p = 0.007). There was no statistical difference in ACE genotype frequency between those who climbed to over 8000 m using supplementary oxygen and those who did not (p = 0.267). This study demonstrates an association between the ACE I-allele and successful ascent to over 8000 m.
Thompson
Julian
J
UCL Institute for Human Health and Performance, London, United Kingdom. julianthompson@doctors.net.uk
Raitt
James
J
Hutchings
Lynn
L
Drenos
Fotios
F
Bjargo
Eirik
E
Loset
Are
A
Grocott
Mike
M
Montgomery
Hugh
H
D000328:Adult; D000483:Alleles; D000531:Altitude; D000532:Altitude Sickness / Q000235:genetics*; D005838:Genotype; D006801:Humans; D016015:Logistic Models; D008297:Male; D009051:Mountaineering; D007703:Peptidyl-Dipeptidase A / Q000235:genetics*; D011110:Polymorphism, Genetic; D012016:Reference Values; D012720:Severity of Illness Index
D007703:Peptidyl-Dipeptidase A