Influence of a high-altitude hypoxic environment on human plasma microRNA profiles

Abstract

Circulating microRNAs (miRNAs) are promising disease biomarkers. However, the influence of high-altitude hypoxic environments on plasma miRNA profiles remains unknown. This study included a total of 509 plasma samples from 278 native Tibetans and 80 newly arrived migrant Han Chinese (Tibet Han) residing at 3560 m and 151 Han Chinese residing at 8.9 m (Nanjing Han). The levels of 754 miRNAs were initially determined using a TaqMan Low Density Array (TLDA) in two pooled samples from 50 Tibet Han and 50 Nanjing Han individuals. Some markedly altered miRNAs in Tibet Han were subsequently measured in all 509 plasma samples by individual qRT-PCR. Compared with the Nanjing Han, 172 miRNAs were differentially expressed in the Tibet Han (105 upregulated and 67 downregulated). The correlation coefficient for the two groups was 0.72. Several upregulated miRNAs were randomly selected for analysis by qRT-PCR, and the results were consistent with those identified by TLDA. These miRNAs were also significantly increased in the Tibetans compared with the Nanjing Han. Furthermore, these altered miRNAs showed strong positive correlations with red blood cell counts and hemoglobin values. These data are the first to provide clear evidence that a high-altitude hypoxic environment significantly affects human plasma miRNA profiles.

Figure 1. Pearson correlation scatter plot of plasma miRNA levels in the Tibet Han and Nanjing Han groups as determined by TLDA.

Figure 2. The relative concentrations of miR-130a-3p, miR-302b-5p, miR-572 and miR-629-5p in the plasma samples from the Nanjing Han (n = 151), Tibet Han (n = 80) and Tibetan (n = 278) groups (A–D).

Cq values were converted to relative concentrations normalized to MIR2911 values and were calculated using the comparative Cq method (2^−ΔCq). Each point represents the mean of triplicate samples. ^*P < 0.05; ^***P < 0.0001.