Analysis of High-altitude Syndrome and the Underlying Gene Polymorphisms Associated with Acute Mountain Sickness after a Rapid Ascent to High-altitude

Abstract

To investigated the objective indicators and potential genotypes for acute mountain sickness (AMS). 176 male subjects were evaluated for symptoms scores and physiological parameters at 3700 m. EPAS1 gene polymorphisms were explored and verified effects of potential genotypes on pulmonary function by inhaled budesonide. The incidence of AMS was 53.98% (95/176). The individuals who suffered from headache with anxiety and greater changes in heart rate (HR), the forced vital capacity (FVC), and mean flow velocity of basilar artery (Vm-BA), all of which were likely to develop AMS. The rs4953348 polymorphism of EPAS1 gene had a significant correlation with the SaO2 level and AMS, and a significant difference in the AG and GG genotype distribution between the AMS and non-AMS groups. The spirometric parameters were significantly lower, but HR (P = 0.036) and Vm-BA (P = 0.042) significantly higher in the AMS subjects with the G allele than those with the A allele. In summary, changes in HR (≥82 beats/min), FVC (≤4.2 Lt) and Vm-BA (≥43 cm/s) levels may serve as predictors for diagnosing AMS accompanied by high-altitude syndrome. The A allele of rs4953348 is a protective factor for AMS through HR and Vm-BA compensation, while the G allele may contribute to hypoxic pulmonary hypertension in AMS.

Figure 1. Changes in arterial blood pressure from 500 m to 3700 m.

SBP, systolic blood pressure; DBP, diastolic blood pressure; MABP, mean arterial blood pressure. **P < 0.01.

Figure 2

(A) Comparison between spirometric parameter and AMS at 3700 m; (B) The comparison between the range of changes in spirometric parameter and AMS after acute exposure to 3700 m. *P < 0.05.

Figure 3. Indicators of acute mountain sickness (AMS).

(A) Correlations of the left ventricular (LV) Tei index, ejection time (ET), heart rate (HR) and mean pulmonary arterial pressure (MABP) with the Lake Louise score (LLS) in all subjects under acute high altitude/hypoxic conditions. (B) Receiver operating characteristic (ROC) curve analysis of the ET (red line), LV Tei index (blue line), HR (purple line) and MABP (green line) was performed to test the diagnostic value of each parameter for AMS diagnosis. (C) Positive correlation between individual changes in serum ACE levels (ng/ml) and LLS after acute exposure to the high altitude (3700 m).

Figure 4

The correlation between AMS and the genotypes of rs2044456 (A) and rs4953348 (B). Significant differences in the SaO2 level were detected in the EPAS1 (rs2044456 and rs4953348) SNP genotypes (P = 0.043 and P = 0.005, respectively).