Evidence for and Against Genetic Predispositions to Acute and Chronic Altitude Illnesses

Abstract

MacInnis, Martin J., and Michael S. Koehle. Evidence for and against genetic predispositions to acute and chronic altitude illnesses. High Alt Med Biol. 17:281-293, 2016.-Humans exhibit marked variation in their responses to hypoxia, with susceptibility to acute and chronic altitude illnesses being a prominent and medically important example. Many have hypothesized that genetic differences are the cause of these variable responses to hypoxia; however, until recently, these hypotheses were based primarily on small (and sometimes anecdotal) reports pertaining to apparent differences in altitude illness susceptibility between populations, the notion that a history of altitude illness is indicative of subsequent risk, the heritability of hypoxia-related traits, and candidate gene association studies. In the past 5 years, the use of genomic techniques has helped bolster the claim that susceptibility to some altitude illnesses is likely the result of genetic variation. For each of the major altitude illnesses, we summarize and evaluate the evidence stemming from three important characteristics of a genetic trait: (1) individual susceptibility and repeatability across assessments, (2) biogeographical differences and familial aggregation, and (3) association(s) with genetic variants. Evidence to support a genetic basis for susceptibilities to acute mountain sickness (AMS) and high-altitude cerebral edema (HACE) is limited, owing partially to the subjective and unclear phenotype of AMS and the rarity and severity of HACE. In contrast, recent genomic studies have identified genes that influence susceptibility to high-altitude pulmonary edema, chronic mountain sickness, and high-altitude pulmonary hypertension. The collection of more individual, familial, and biogeographical susceptibility data should improve our understanding of the extent to which genetic variation contributes to altitude illness susceptibility, and genomic and molecular investigations have the potential to elucidate the mechanisms that underpin altitude illness susceptibility.

Acute mountain sickness, arterial oxygen saturation and heart rate among Tibetan students who reascend to Lhasa after 7 years at low altitude: a prospective cohort study

“…However, these genes have been related to chronic mountain sickness, and as far as we know, no direct evidence between these genes and AMS has been proposed. 38 39 Although it seems likely that genetics plays a role in the development of AMS, we cannot fully decide whether the observed differences between Tibetan and Han Chinese students can be explained by genetic background. It has been reported that lowlanders with a pre-exposure to high altitude may establish some degree of physiological adaptation, thus resulting in a reduction in the incidence and severity of AMS when they reascend to high altitude.…”

The relationship between anxiety and acute mountain sickness

“…It is interesting that trait STAI Y-2 scores and not state STAI Y-1 scores, taken at the study baseline altitude of 848m, were predictive of future risk of severe AMS. This is perhaps not surprising, given that susceptibility to AMS appears to be a relatively stable individual trait with increasing evidence for a genetic predisposition that can be influenced by additional factors such as ascent profile [ 28 – 30 ]. We found that trait anxiety and STAI Y-2 questions, as opposed to STAI Y-1 was a predictor of future AMS given its representation of more stable individual trait anxiety levels [ 23 ].…”

Differences in Tolerance to Hypoxia: Physiological, Biochemical, and Molecular-Biological Characteristics

“…In addition, the presence of numerous polymorphisms of the HIF1A gene and dependent genes indicates some genetic determinism of tolerance to hypoxia [ 16 , 80 ]. The presence of HIF1A gene polymorphisms in humans, which determines the high level of HIF-1α expression and functional activity, can contribute to growth in an aerobic capacity and the organism’s adaptation to hypoxia and physical activities [ 81 , 82 , 83 , 84 ].…”

“…Oxygen deficiency is one of the key factors in the development of infectious, inflammatory, and tumor diseases [ 1 , 2 , 3 , 4 , 5 , 6 ]. It is known that basic tolerance to hypoxia in humans and various animal species differs [ 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 ]. The differences in basic tolerance to oxygen deficiency can determine the predisposition to the development of hypoxia-related disorders.…”