Comparative analysis of high altitude hypoxia induced erythropoiesis and iron homeostasis in Indian and Kyrgyz lowlander males

Abstract

Lowland residents acclimatize to reduced oxygen availability at high altitude by certain functional alterations in body which vary according to the different lifestyle, geographical location, ethnicity etc. In our study, two different ethnic lowlander groups acclimatization response was investigated during high altitude exposure. Overnight fasting blood of Indian (n = 20) and Kyrgyz (n = 20) at baseline and high altitude (4,111 m) day 3, 7, 14, 21 was collected and analysed. High altitude induced erythropoiesis was higher in Indians compared to Kyrgyz. Hemoglobin, hematocrit, red blood cells increased till high altitude day 21 and erythropoietin till day 7 in Indians. Hepcidin decrease was double in Indians compared with Kyrgyz and iron, ferritin and transferrin receptor were found synchronized to maintain circulatory iron for erythropoiesis. Further to validate, RNA sequencing analysis of differentially expressed gene by DAVID hit hematopoietic cell lineage among top up regulated pathway in Indian vs Kyrgyz. IPA analysis disclosed GATA1 as second most top upstream regulator in Indians as compared to Kyrgyz at high altitude day7 and activation of haematological system development and function at HAD14 in Indian vs Kyrgyz. Valedictory qRT-PCR for putative genes like HAMP, BMP6, EPOR, etc. indicated differences in erythroid and iron regulation in both. Our data strongly reflected different erythropoietic response towards altitude exposure in two different ethnic lowlanders.

Keywords

• High altitude
• Ethnicity
• RNA sequencing
• Erythropoiesis
• Hepcidin
• Acclimatization