Hemoglobin concentration of high-altitude Tibetans and Bolivian Aymara

Abstract

Elevated hemoglobin concentrations have been reported for high-altitude sojourners and Andean high-altitude natives since early in the 20th century. Thus, reports that have appeared since the 1970s describing relatively low hemoglobin concentration among Tibetan high-altitude natives were unexpected. These suggested a hypothesis of population differences in hematological response to high-altitude hypoxia. A case of quantitatively different responses to one environmental stress would offer an opportunity to study the broad evolutionary question of the origin of adaptations. However, many factors may confound population comparisons. The present study was designed to test the null hypothesis of no difference in mean hemoglobin concentration of Tibetan and Aymara native residents at 3,800-4,065 meters by using healthy samples that were screened for iron deficiency, abnormal hemoglobins, and thalassemias, recruited and assessed using the same techniques. The hypothesis was rejected, because Tibetan males had a significantly lower mean hemoglobin concentration of 15.6 gm/dl compared with 19.2 gm/dl for Aymara males, and Tibetan females had a mean hemoglobin concentration of 14.2 gm/dl compared with 17.8 gm/dl for Aymara females. The Tibetan hemoglobin distribution closely resembled that from a comparable, sea-level sample from the United States, whereas the Aymara distribution was shifted toward 3-4 gm/dl higher values. Genetic factors accounted for a very high proportion of the phenotypic variance in hemoglobin concentration in both samples (0.86 in the Tibetan sample and 0.87 in the Aymara sample). The presence of significant genetic variance means that there is the potential for natural selection and genetic adaptation of hemoglobin concentration in Tibetan and Aymara high-altitude populations.

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

“…In absolute terms, these differences were several fold larger than for any of the determinants of hemoglobin concentration in populations residing at low altitude (31-34). Our findings are, however, consistent with previous high estimates of heritability (h 2 ) for hemoglobin concentration of 0.66 among Tibetans at 4,850-5,450 m (36) and of 0.86 among Tibetans at 3,800-4,065 m (15). These values estimate the proportion of additive genetic variation relative to total phenotypic variance.…”

“…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.…”

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

“…However, if genetic adaptations have occurred in human high altitude natives, they do not seem to be manifested in Hb or [2, changes. Tibetans and Andeans are reported to have normal Hb A (Beall et al, 1998), and high altitude natives have been shown to have increased [2,, which is associated with a rightward shift of the ODC (Torrance et al, 1970b). …”

Native highland and lowland populations differ in .GAMMA.-globin gene promoter polymorphisms related to altered fetal hemoglobin levels and delayed fetal to adult globin switch after birth

“…Since oxygen is reversibly bound to hemoglobin, hemoglobin genes are possible candidates for genetic adaptation to high altitude. The high heritability for hemoglobin concentration of 0.89 in Andean populations suggests a strong genetic influence (Beall et al, 1998).…”