Role of Mitochondrial tRNA ^Leu 12320 A>G Mutation on Heart Rate Variability and Blood Pressure at Low-Altitude and in a High-Altitude Hypoxic Environment

Pan, Cuiping, Qunyuan Wang, Minglei Zhang, Ruizhe Li, Yining Liu, and Zongbin Li. Role of Mitochondrial tRNA Leu 12320 A>G Mutation on Heart Rate Variability and Blood Pressure at Low Altitude and in a High-Altitude Hypoxic Environment. High Alt Med Biol. 00:00–00, 2025. Introduction: Mutations—gene mutations—can exert dual, environment-dependent effects on cardiovascular disease. Materials and Methods: We analyzed clinical data and mitochondrial DNA from 84 young Han Chinese men ascending from low-altitude to high-altitude regions (>4,000 m). Results: Nine subjects harbored the mitochondrial tRNA A12320G mutation. Notably, none of these 9 mutation carriers developed acute mountain sickness (AMS), whereas 34 (40.5%) of the 84 volunteers in the cohort were diagnosed with AMS, indicating a significant protective association ( p = 0.009 ). In the low-altitude environment, time domain parameters of heart rate variability (HRV) in the mutant volunteers were significantly lower than those in the unmutated volunteers (SDNN: 141.76 ± 30.75 ms vs.169.08 ± 32.83 ms, p = 0.020; RMSSD: 29.70 ms vs. 41.35 ms, p = 0.022; HRV triangular index: 41.8% vs. 52.4%, p = 0.024; SDSD: 37.4 ms vs. 50.5 ms, p = 0.016; PNN50: 3.1% vs 7.6%, p = 0.008); 24-hour mean systolic blood pressure (118.63 ± 9.54 vs. 113.39 ± 6.30 mmHg, p = 0.029), nocturnal mean diastolic blood pressure (67.37 ± 7.91 vs. 61.11 ± 7.08 mmHg, p = 0.015) were also higher; HRV and blood pressure were not statistically different between the mutant and nonmutant groups in the high-altitude environment. Hematological analysis revealed mutants at high altitude had significantly lower plateletcrit (0.23% vs. 0.26%, p = 0.019) and total protein (72.78 ± 3.84 g/L vs.75 .65 ± 3.0 g/L, p = 0.008). Conclusion: The A12320G mutation acts as a cardiovascular risk factor (reduced HRV, increased blood pressure) at low altitude, whereas at high altitude it was associated with a reduced incidence of AMS, possibly through metabolic adaptive mechanisms, reflecting the environmentally dependent dual roles of this gene effect.