Lessons in hypoxic adaptation from high-altitude populations

Abstract

An increase in hemoglobin level is seen in virtually all lowlanders who move to or train at altitude; however, studies of high-altitude native populations illustrate that this response is not necessary for successful long-term residence. Indigenous populations living at the same altitude have differences not only in hemoglobin level but also in other traits like oxygen saturation. Support for a genetic causation for differences in features of oxygen transport, namely hemoglobin levels and oxygen saturation, is derived from kindred studies among the highlander populations. Indeed, evidence from Tibet suggests that inferred genes for high oxygen saturation are associated with higher offspring survival. It may be that signaling molecules like nitric oxide and transcription factors such as hypoxia-inducible factor could act as an upstream regulator for highlander traits. However, the preponderance of data suggests that it is unlikely that one process or even a common set of processes is responsible for successful biologic adaptation shown in all three resident high-altitude populations. Future studies will require the ability to identify combinations of genetic variants with outcomes including expression levels, appropriate phenotypes, and functional responses.

King of the Mountains: Tibetan and Sherpa Physiological Adaptations for Life at High Altitude

“…Aside from HIF, other gene regions have been studied. The insertion allele (I) of the ACE gene is associated with low serum levels of ACE and has been described as a marker of successful adaptation to hypoxia (144). Although it therefore seems plausible that the I allele's presence is essential in the genotype of those thriving at high altitude (39,101), no allele overrepresentation was seen in Sherpas (147).…”

SNPs, Linkage Disequilibrium and Transcriptional Factor Binding Sites Associated with Acute Mountain Sickness among Han Chinese at the Qinghai-Tibetan Plateau

“…The illness will resolve itself if no additional altitude is attempted; however, in some cases the descent to a lower altitude is necessary in order to reverse the condition. The precise pathogenesis of AMS is not well understood, but hypoxia is considered to be the major factor [4][5][6][7], which raises the question of why some individuals are susceptible to the sickness while others are not, under the same high altitude environment.In an effort to provide in cite into this question, we have previously published on known genetic associations of simple nucleotide polymorphisms (SNPs) with high altitude sickness [8][9][10][11]. In the present study, we examine the interaction of seventeen SNPs in nine genes [8][9][10][11] with regard to AMS and the effect these SNPs have on potential changes in transcriptional factor binding sites (TFBS).…”

SNPs and TFBS Associated with High Altitude Sickness*

“…CMS is a syndrome resulting from the loss of human adaptation to high altitude and can occur in permanent residents residing in this environment [20,21]. The precise pathogenesis of AMS and CMS is not well understood, but hypoxia is likely to be a major factor [22][23][24][25][26]. This raises the question of why some individuals are susceptible to AMS and CMS while others are not, under the same hypoxic conditions.…”