Li Zongbin, Liu Chunwei, Guo Jun, Shi Yajun, Li Yang, Wang Jinli, Zhou Shanshan, Chen Yundai
Department of Cardiology, The Sixth Medical Center of Chinese PLA General Hospital, Beijing, China.
The Second School of Clinical Medicine, Southern Medical University, Guangzhou, China.
Front Cardiovasc Med. 2022 Feb 25;9:832136. doi: 10.3389/fcvm.2022.832136. eCollection 2022.
Acute exposure to hypobaric hypoxia can trigger acute mountain sickness (AMS), while the exact mechanism has not been fully revealed. The role of genetic factors in the susceptibility of various high-altitude diseases has also gained much interest. Previous studies have provided evidence for the link between AMS and certain nuclear genes or mitochondrial haplogroup. The correlation between point mutations of mitochondrial DNA (mtDNA) and AMS was further explored in the present study.
A total of 84 young Han males residing at low altitude were taken to an elevation of 4,000 m within 40 h. We collected data of their heart rate, blood pressure, peripheral oxygen saturation (SaO), and obtained blood samples, at sea level and at high altitude. AMS was diagnosed using the revised version of the Lake Louise Questionnaire Score. Sequencing was utilized to identify the association between mtDNA alleles and the occurrence of AMS. We also assessed the association between the presence of AMS and physiological variables, and provided a preliminary discussion of the association between genotypic and phenotypic variation.
The percentage of neutrophils [Odds ratio (OR): 1.06, 95% confidence interval (CI): 1.01-1.12, = 0.034) and SaO level (OR: 0.87, 95% CI: 0.79-0.95, = 0.004) were independently associated with the development of AMS. A4576G was a risk factor for AMS (OR: 6.27, 95% CI: 1.2-32.7). T11613C (OR: 0.10, 95% CI: 0.01-0.83), A8923G (OR: 0.15, 95% CI: 0.03-0.76), and T5543C (OR: 0.19, 95% CI: 0.04-0.95) were protective factors for AMS. The level of SaO was significantly lower in the individual with A4576G mutation as compared with the individual without A4576G mutation (68.1 ± 7.9 vs. 75.8 ± 6.1, = 0.001). The level of serum sodium was significantly higher in the individual with A8923G mutation as compared to the individual without A8923G mutation (144.6 ± 1.9 vs. 143.2 ± 1.9, = 0.027).
The increase in neutrophils and the disability to preserve oxygen saturation may be associated with the high altitude intolerance in young Chinese Han males. A4576G is the risk factor for AMS. T11613C, A8923G, and T5543C are protective factors for AMS. The role of A8923G mutation may correlate with the sodium and water balance and the role of the A4576G mutation may be related to the disability to maintain blood oxygen level after quickly entering the plateau.
急性低压低氧暴露可引发急性高原病（AMS），但其确切机制尚未完全阐明。遗传因素在各种高原病易感性中的作用也备受关注。既往研究已为AMS与某些核基因或线粒体单倍群之间的联系提供了证据。本研究进一步探讨线粒体DNA（mtDNA）点突变与AMS的相关性。
选取84名居住在低海拔地区的年轻汉族男性，在40小时内将其带至海拔4000米处。我们在海平面和高海拔地区收集他们的心率、血压、外周血氧饱和度（SaO）数据，并采集血样。使用修订版的路易斯湖问卷评分诊断AMS。采用测序法确定mtDNA等位基因与AMS发生之间的关联。我们还评估了AMS的存在与生理变量之间的关联，并对基因型和表型变异之间的关联进行了初步讨论。
中性粒细胞百分比[比值比（OR）：1.06，95%置信区间（CI）：1.01 - 1.12，P = 0.034]和SaO水平（OR：0.87，95%CI：0.79 - 0.95，P = 0.004）与AMS的发生独立相关。A4576G是AMS的危险因素（OR：6.27，95%CI：1.2 - 32.7）。T11613C（OR：0.10，95%CI：0.01 - 0.83）、A8923G（OR：0.15，95%CI：0.03 - 0.76）和T5543C（OR：0.19，95%CI：0.04 - 0.95）是AMS的保护因素。与无A4576G突变的个体相比，有A4576G突变的个体的SaO水平显著更低（68.1±7.9对75.8±6.1，P = 0.001）。与无A8923G突变的个体相比，有A8923G突变的个体的血清钠水平显著更高（144.6±1.9对143.2±1.9，P = 0.027）。
中性粒细胞增多和无法维持血氧饱和度可能与中国年轻汉族男性的高原不耐受有关。A4576G是AMS的危险因素。T11613C、A8923G和T5543C是AMS的保护因素。A8923G突变的作用可能与钠水平衡相关，而A4576G突变的作用可能与快速进入高原后维持血氧水平的能力有关。
