Angiotensin converting enzyme insertion allele in relation to high altitude adaptation

Abstract

Angiotensin converting enzyme (ACE) gene I\D polymorphism has been associated with high altitude (HA) disorders as well as physical performance. We, however, envisage that the polymorphism may be associated with adaptation to the hypobaric hypoxia of altitude, thus facilitating physical performance. For this purpose, three unrelated adult male groups, namely (1) the Ladakhis (HLs), who reside at and above a height of 3600 m, (2) lowlanders, who migrated to Ladakh (MLLs), and (3) resident lowlanders (LLs), have been investigated. The HLs had significantly ( p 0n001) greater numbers of the II homozygotes and the ID heterozygotes than the DD homozygotes, the genotype distribution being 0n46, 0n43 and 0n11 for II, ID and DD genotypes respectively. The MLLs comprised 60 % II homozygotes, which was higher ( p 0n001) than the HLs (46 %). In the LLs, the heterozygotes were greater ( p 0n001) in number than the II and DD homozygotes. The I allele frequency was 0n72 in the MLLs, 0n67 in the HLs and 0n55 in the LLs. Polymorphism study suggested that the II genotype could be associated with altitude adaptation, which might influence physical efficiency. People living at sea level experience various levels of physical discomfort at high altitude (HA) due to hypobaric hypoxia and cold. The effects of hypoxia on cardio-pulmonary function (Sutton et al. 1988 ; Mirrakhimov & Winslow, 1996) are most evident during hard physical work when the already taxed oxygen transport system needs to meet increased metabolic demands. This results in somewhat reduced levels of performance of individuals when faced with tasks demanding high levels of physical and mental performance. However, long-term in-

Effect of aging on blood pressure in Leh, Ladakh, a high-altitude (3524 m) community, by comparison with a Japanese town

“…This difference may result in an exaggerated increase in systolic and diastolic BP with age, as well as with a higher diastolic BP at rest, compared to Japanese people [3]. Fifth, angiotensin-converting-enzyme gene I/D polymorphism is reportedly associated with highaltitude disorders as well as with differences in physical performance [4][5][6]. It is also speculated that this polymorphism may be related to the larger increase in BP with age observed herein.…”

Adaptation to High Altitude in Sherpas: Association with the Insertion/Deletion Polymorphism in the Angiotensin-Converting Enzyme Gene

“…38 Whatever the race, individuals with II genotype have the lowest circulating ACE levels, DD homozygotes have the highest ACE levels, and ID heterozygotes have intermediate levels. 9,10,38 One outstanding study demonstrated an allele skew with a significant excess of the I allele and II genotype in elite male British mountaineers who ascended beyond 7,000 m without the use of supplemental oxygen. 12 Following a line of this study, it was shown that the I allele of the ACE gene is associated with maintenance of SpO 2 during rapid ascent to altitudes over 5,000 m. 39 Regarding high-altitude residents, Qadar Pasha et al 10 reported that the I allele and II genotype of ACE I/D polymorphism were significantly prevalent in high-altitude natives of Ladakhis, who reside for their lifetime at over 3600 m compared to lowland residents in the same region.…”

“…[9][10][11] The ACE gene is chosen primarily as a candidate gene because the I allele has been shown to be associated with Caucasian mountain climbers who ascended to extremely high altitude without supplemental oxygen. 12 The objective of this study was to investigate ACE I/D polymorphism in Sherpas in order to evaluate the possible involvement of this polymorphism in high altitude adaptation in Sherpas.…”

Genomic analysis of snub-nosed monkeys (Rhinopithecus) identifies genes and processes related to high-altitude adaptation

“…ARNT (SG specific), whose protein product binds to HIF-α to regulate adaptation to hypoxia 37 , has been mentioned as a target of positive selection in the human Tibetan population 45 . ACE (SG specific), which functions in blood pressure regulation and carries variants responsible for high-altitude pulmonary hypertension (HAPH) 38 , has been reported to have a role in high-altitude adaptation of human populations [46][47][48] . In comparison, no significant signatures of selection were observed in hemoglobin genes, which have been identified as critical genes for oxygen binding and resistance to hypoxia in other high-altitude mammals [49][50][51][52][53] .…”