Global expression profiling and pathway analysis in two different population groups in relation to high altitude

• Published in: Functional & integrative genomics 2019, Vol.19 (1), p.205-215
• Main Authors: Saini, Supriya, Vats, Praveen, Bayen, Susovon, Gaur, Priya, Ray, Koushik, Kishore, Krishna, Sartmyrzaeva, Meerim, Akunov, Almaz, Maripov, Abdirashit, Sarybaev, Akpay, Kumar, Bhuvnesh, Singh, Shashi Bala
• Format: Article
• Language: English
• Subjects: Adenosine; Altitude; Animal Genetics and Genomics; Biochemistry; Bioinformatics; Biomedical and Life Sciences; CD73 antigen; Cell Biology; Cyclic AMP; Gene expression; Hypoxia; Life Sciences; Microbial Genetics and Genomics; Nucleotides; Original Article; Plant Genetics and Genomics; Population; Ribonucleic acid; Ribosomal proteins; RNA; Signal transduction
• ISSN: 1438-793X; 1438-7948
• DOI: 10.1007/s10142-018-0637-5

High altitude (HA) is associated with number of stresses. Response of these stresses may vary in different populations depending upon altitude, duration of residency, ancestry, geographical variation, lifestyle, and ethnicities. For understanding population variability in transcriptome, array-based global gene expression profiling was performed on extracted RNA of male volunteers of two different lowland population groups, i.e., Indians and Kyrgyz, at baseline and day 7 of HA exposure (3200 m). A total of 97 genes were differentially expressed at basal in Kyrgyz as compared to Indians (82 downregulated and 15 upregulated), and 196 were differentially expressed on day 7 of HA (118 downregulated and 78 upregulated). Ingenuity Pathway Analysis and gene ontology highlighted eIF2 signaling with most significant negative activation z score at basal in Kyrgyz compared to Indians with downregulation of various L- and S-ribosomal proteins indicating marked translational repression. On day 7, cAMP-mediated signaling is most enriched with positive activation z score in Kyrgyz compared to Indians. Plasma cAMP levels were higher in Kyrgyz on day 7 compared to Indians. Extracellular adenosine levels were elevated in both the groups upon HA, but higher in Kyrgyz compared to Indians. Valedictory qRT-PCR showed upregulation of ADORA2B and CD73 along with downregulation of ENTs in Kyrgyz compared to Indians indicating elevated levels of extracellular nucleotides mainly adenosine and activation of extracellular cAMP-adenosine pathway which as per literature triggers endogenous protective mechanisms under stress conditions like hypoxia. Thus, transcriptome changes at HA are population-specific, and it may be necessary to take care while interposing similar results in different populations.