Effect of EGLN1 Genetic Polymorphisms on Hemoglobin Concentration in Andean Highlanders

Yoshiki Yasukochi,Kiyoshi Aoyagi,Victor Mendoza,Hideki Fukuda,Mika Nishihara,Guillermo Alvarez,Juan Ugarte,Mayumi Ohnishi,Takayuki Nishimura,Marco Fichera

doi:10.1155/2020/3436581

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.

Highlights

Physiological phenotypes of the ancestors of modern humans adapted to various new environments across the world through genetic changes affecting their adaptive phenotypes [1,2,3,4,5]
Tibetan highlanders have a moderate Hb concentration that is comparable to that of individuals residing at sea-level because of increased plasma volume, and this may be an adaptive advantage in high-altitude environments as it results in a lower blood viscosity promoting blood flow and oxygen delivery, protection against polycythemia due to elevated red blood cell volume, and enhanced exercise capacity [11, 12, 15,16,17]
In a Bolivian cohort of 99 healthy men and women, we found that the estimated egl-9 family hypoxia inducible factor 1 (EGLN1) haplotype frequencies were significantly correlated with Hb levels in the Bolivians

Summary

Introduction

Physiological phenotypes of the ancestors of modern humans adapted to various new environments across the world through genetic changes affecting their adaptive phenotypes [1,2,3,4,5]. High-altitude environments are extreme due to hypobaric hypoxia conditions. To understand human tolerance to such severe conditions, many studies have investigated the intrinsic physiological traits of modern humans who have settled at high altitudes, Andean, Ethiopian, and Tibetan populations [6,7,8,9,10,11,12]. Tibetan highlanders have a moderate Hb concentration that is comparable to that of individuals residing at sea-level because of increased plasma volume, and this may be an adaptive advantage in high-altitude environments as it results in a lower blood viscosity promoting blood flow and oxygen delivery, protection against polycythemia due to elevated red blood cell volume, and enhanced exercise capacity [11, 12, 15,16,17]

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