Effect of EGLN1 Genetic Polymorphisms on Hemoglobin Concentration in Andean Highlanders

Abstract

The physiological characteristics of Andean natives living at high altitudes have been investigated extensively, with many studies reporting that Andean highlanders have a higher hemoglobin (Hb) concentration than other highlander populations. It has previously been reported that positive natural selection has acted independently on the egl-9 family hypoxia inducible factor 1 (EGLN1) gene in Tibetan and Andean highlanders and is related to Hb concentration in Tibetans. However, no study has yet revealed the genetic determinants of Hb concentration in Andeans even though several single-nucleotide polymorphisms (SNPs) in EGLN1 have previously been examined. Therefore, we explored the relationship between hematological measurements and tag SNPs designed to cover the whole EGLN1 genomic region in Andean highlanders living in Bolivia. Our findings indicated that haplotype frequencies estimated from the EGLN1 SNPs were significantly correlated with Hb concentration in the Bolivian highlanders. Moreover, we found that an Andean-dominant haplotype related to high Hb level may have expanded rapidly in ancestral Andean highlander populations. Analysis of genotype data in an ~436.3 kb genomic region containing EGLN1 using public databases indicated that the population structure based on EGLN1 genetic markers in Andean highlanders was largely different from that in other human populations. This finding may be related to an intrinsic or adaptive physiological characteristic of Andean highlanders. In conclusion, the high Hb concentrations in Andean highlanders can be partly characterized by EGLN1 genetic variants.

Individual variations and sex differences in hemodynamics and percutaneous arterial oxygen saturation (SpO2) in Tibetan highlanders of Tsarang in the Mustang district of Nepal

“…Although populational differences have been well discussed, there is limited knowledge of physiological variations in highlanders [ 3 , 10 ]. From the perspective of physiological anthropology, various studies have conducted field research to investigate variation in physiological response from the perspective of acute hypobaric hypoxia in lowlanders [ 11 , 12 ] or of physiological variation in highlanders [ 6 , 13 , 14 ]. In our previous field research, we investigated the health status of Tibetans in Tsarang village (altitude, 3570 m) [ 6 ].…”

Insight into the Effects of High-Altitude Hypoxic Exposure on Learning and Memory

“…Another gene that has attracted widespread attention is Egl nine homolog 1 (EGLN1), which encodes proline hydroxylase 2 (PHD2). The EGLN1 mutations in Tibetans lead to increased degradation of HIF in the body under hypoxia conditions, thereby preventing the production of excessive red blood cells and reducing the risk of prenatal death, heart disease, and stroke [19][20][21]. Even though the Tibetans have adapted to the plateau environment, they could still suffer from the effects of hypoxia on the plateau.…”

The Comparison of Hemoglobin Levels, Blood Oxygen Saturation, and Breaths Frequency on The Lowlander and Highlander

“…Karena pertukaran gas pada alveolus semakin sulit dengan bertambahnya ketinggian (Juniati et al, 2021;Sharp et al, 2021), maka tubuh melakukan adaptasi morfologis dengan cara memperbesar rongga dada dan meningkatkan kekuatan otot-otot pernafasan (Hastuti, 2007). Selain itu, juga terjadi adaptasi fisiologis berupa peningkatan kadar hemoglobin darah (Foss dan Keteyian, 1998;Yasukochi et al, 2020). Hal ini diduga akan berkorelasi dengan frekuensi nafas dalam satu menit yang dibutuhkan dan jumlah saturasi oksigen dalam darah.…”