Different hematologic responses to hypoxia in Sherpas and Quechua Indians

Abstract

Previous studies of the erythropoietic response to hypoxia in high-altitude natives suggest that the hematocrit and hemoglobin values in Himalayan natives (Sherpas) are lower than expected for the altitude, perhaps because of a genetic adaptation. However, differences in sampling techniques and experimental methods make comparisons difficult. Our studies were carried out to compare the erythropoietic response with the same altitude in age-matched natives of the Himalayas and Andes by the same experimental techniques. Healthy male subjects were selected in Ollagüe, Chile (n = 29, 27.3 +/- 5.9 yr) and in Khunde, Nepal (n = 30, 24.7 +/- 3.8 yr). Both of these villages are located at 3,700 m above sea level. Hematologic measurements confirmed lower hematocrit values in Nepal (48.4 +/- 4.5%) than in Chile (52.2 +/- 4.6%) (P less than 0.003). When subjects were matched for hematocrit, erythropoietin concentrations in Chile were higher than in Nepal (P less than 0.01). Detailed measurements of blood O2 affinity in Nepal showed no differences in shape or position of the O2 equilibrium curve between Sherpas and Western sojourners. Our results indicate that although Quechua Indians have higher hematocrits than Sherpas living at the same altitude, nevertheless they may be functionally anemic.

The in-vivo oxyhaemoglobin dissociation curve at sea level and high altitude

“…As with the instances above of acclimatized lowlanders, the similarity between the P 50 values of the high altitude natives and sea level controls was attributed to an in vivo balance of the influences of alkalosis and increased [2,3-DPG] on the affinity of Hb for O 2 . A later study by Winslow et al (1989) showed similar results in a group of high altitude Sherpas living at 3700 m, whose physiological ODCs were not shifted as compared to controls.…”

Phenotypic plasticity and genetic adaptation to high-altitude hypoxia in vertebrates

“…The studies by Beall et al (Beall et al, 2010) and Yi et al (Yi et al, 2010) revealed a striking signal of positive selection at EPAS1, and documented that noncoding nucleotide variants in and around the EPAS1 gene are strongly associated with a reduced Hb concentration in Tibetan highlanders. Previous studies demonstrated that Tibetan highlanders are characterized by low Hb concentrations relative to acclimatized lowlanders, as well as to Andean highlanders that are resident at comparable altitudes (Beall and Reichsman, 1984;Winslow et al, 1989;Beall et al, 1990;Beall et al, 1998;Garruto et al, 2003;Wu et al, 2005;Beall, 2007). Remarkably, Tibetans living at elevations of up to 4000m present a hematological profile similar to what would be expected at sea level.…”

Natural selection on EPAS1 ( HIF2α ) associated with low hemoglobin concentration in Tibetan highlanders

“…Typically, Tibetans average at least 1 g/dL and as much as approximately 3.5 gm/dL (i.e. approximately 10-20%) lower hemoglobin concentration in comparison with their Andean counterparts (14)(15)(16) or acclimatized lowlanders, such as the Han who have moved to altitudes above 2,500 m (4,(17)(18)(19)(20)(21)(22)(23). This suggests that Tibetans have evolved a blunted erythropoietic response to high-altitude hypoxia.…”