Division of Respiratory Medicine, Department of Pediatrics, University of California San Diego, 9500 Gilman Drive, MC 0735, La Jolla, CA, 92093, USA.
Department of Computer Science and Engineering, University of California San Diego, La Jolla, CA, 92093, USA.
J Mol Med (Berl). 2017 Dec;95(12):1269-1282. doi: 10.1007/s00109-017-1584-7. Epub 2017 Sep 26.
About 1.2 to 33% of high-altitude populations suffer from Monge's disease or chronic mountain sickness (CMS). Number of factors such as age, sex, and population of origin (older, male, Andean) contribute to the percentage reported from a variety of samples. It is estimated that there are around 83 million people who live at altitudes > 2500 m worldwide and are at risk for CMS. In this review, we focus on a human "experiment in nature" in various high-altitude locations in the world-namely, Andean, Tibetan, and Ethiopian populations that have lived under chronic hypoxia conditions for thousands of years. We discuss the adaptive as well as mal-adaptive changes at the genomic and physiological levels. Although different genes seem to be involved in adaptation in the three populations, we can observe convergence at genetic and signaling, as well as physiological levels. What is important is that we and others have shown that lessons learned from the genes mined at high altitude can be helpful in better understanding and treating diseases that occur at sea level. We discuss two such examples: EDNRB and SENP1 and their role in cardiac tolerance and in the polycythemic response, respectively.
约 1.2%至 33%的高原人群患有 Monge 病或慢性高山病（CMS）。年龄、性别和原籍人群等多种因素（年龄较大、男性、安第斯人）导致从各种样本报告的百分比有所不同。据估计，全世界有大约 8300 万人生活在海拔 > 2500 米的地区，面临 CMS 的风险。在这篇综述中，我们关注的是世界各地各种高海拔地区的人类“自然实验”，即安第斯、西藏和埃塞俄比亚人群，他们已经在慢性缺氧环境中生活了数千年。我们讨论了基因组和生理水平上的适应性和不适应性变化。尽管在这三个人群中似乎涉及不同的基因参与适应，但我们可以观察到遗传和信号转导以及生理水平上的趋同。重要的是，我们和其他人已经表明，从高海拔地区挖掘的基因中获得的经验教训有助于更好地理解和治疗海平面上发生的疾病。我们讨论了两个这样的例子：EDNRB 和 SENP1 及其在心脏耐受和多血症反应中的作用。
