Phenotypic Variations Related to Hypoxic Responses Among Andean Highlanders Living at Different Altitudes (400m, 4000m, 5000m)

Introduction

Adaptation to high altitude poses selective evolutionary changes involving multiple and challenging adaptive responses, and one of them deals with the low pressure of oxygen. Native Bolivian Andeans have lived at an average of 3000-5000 m for about 14,000 years, and have developed different erythroid phenotypes compared to other populations living at high altitude (PMID 30781443; PMID 25342802). Although Andeans have developed genetic adaptations related to erythropoiesis regulation (Blood, ASH 2316, 2018) they still undergone with polycythemic states, and those of clinical relevance are often Chronic Mountain Sickness erythrocytosis (CMS-E), secondary erythrocytosis (SE) and polycythemia vera (PV) (Rev Hematol Mex. 2016 Jan;17(1):8-20). Either adaptation or erythrocytosis condition entails important changes in hemoglobin, SpO2, P50 and lactate, so evaluating significant changes among Andeans living at different altitudes as well as the modifications between erythrocytosis patients and healthy highlanders became of interest.

Material and method

We collected venous blood samples from Bolivian native Andeans born at 4000 m (n=124) but living at 3 different altitudes (400 m, 4000 m, 5000 m), aside from Europeans (n=11) residing at 4000 m. Complete blood count, venous blood gas, and oxygen saturation studies were performed. P50 was measured by using a formula described by Lichtman. Likewise, a differential diagnosis regarding healthy inhabitants and polycythemia patients was performed.

Results

In healthy Andean inhabitants in different altitudes, the Hb levels increased at increasing altitude (p:0.001), meanwhile SpO2 (p:0.001) and P50 (p:0.001) decreased. No lactate variations among them were observed (Table 1). European subjects at 4000 m in relation to Andean inhabitants at the same altitude displayed higher Hb levels (p: 0.01), without variations in SpO2 and P50, but a significant increased lactate (p: 0.001) (Table 1).

When comparing healthy subjects and patients with erythrocytosis (CMS-E, SE, PV) at 4000 m, the latter displayed higher Hb levels (p:0.001), decreased SpO2 (p:0.001), no variations in P50, and increased lactate in CMS-E and SE patients (p:0.01) (Table 2). Similarly, patients with erythrocytosis (CMS-E, SE) at 5000 m, related to healthy subjects at the same altitude, reflected increased Hb (p:0.001), decreased SpO2 (p:0.01), P50 without variations, and increased lactate (p:0.01) (Table 2).

Conclusions

Native Andeans from Bolivia born at 4000 m but living at different altitudes have variations regarding hematological phenotypes, decreased P50 shifts the hemoglobin dissociation curve to left.

Patients with erythrocytosis have distinct phenotypes in relation to healthy subjects characterized by decreased saturation and increased lactate.

Higher Hb levels and increased lactate in Europeans living at 4000 m probably due to the different residing time at high altitude, since native Andean inhabited high-altitude regions for many years.

No relevant conflicts of interest to declare.