CYP450基因家族低氧适应相关甲基化位点筛选及表观遗传学机制研究

高原地区的低气压与低氧分压严重地影响人类在高原地区的生存与发展。研究高原低氧反应和低氧适应的分子遗传机制一直以来是受到生物学及医学界关注的重要领域。以往对于高原性疾病的研究认为：低氧适应是一个复杂的性状，人体为了应对低氧，除了激活和稳定转录调控因子外，还会启动一些基因的甲基化等表观调控机制，可导致基因表达的长期改变。我们前期研究结果表明，细胞色素(P-450)酶基因超家族部分基因的甲基化改变参与了高原肺水肿的发生，但其表观调控机制尚未完全清楚。本研究通过使用Sanger测序技术，MassARRAY EpiTYPER DNA甲基化定量分析技术和焦磷酸测序技术分析CYP基因家族基因变异及甲基化对低氧适应和HAPE发生的表观遗传学改变，从表观遗传学角度进一步探索低氧适应和HAPE的致病机制。预期研究结果对于完善高海拔低氧适应的表观遗传学调控提供依据，也为进一步研究低氧适应相关基因提供方向和目标。

Low air pressure and hypoxia seriously affect human survival and development in the plateau area. The molecular genetic mechanism of response to hypoxia and hypoxia adaptation has been an important research area concerned by biology and medicine researchers. In the past, the high altitude disease researchers believed that adaptation to hypoxia is a complex trait, human in response to hypoxia, in addition to the activation and stable transcription factor outside, will due to some genes’ methylation and other epigenetic regulation mechanisms, which can lead to long-term changes in gene expression. Our previous study showed that methylation changes of the cytochrome P-450 enzyme (CYP450) gene in the high-altitude pulmonary edema (HAPE) patients, but the regulatory mechanisms are not yet fully understood. This research, using of Sanger sequencing technology and massarray EpiTYPER quantitative DNA methylation analysis technology and pyrosequencing analysis to detect occurrence of CYP450 genes’ mutation and methylation change relating to hypoxia adaptation and HAPE, and to further explore the pathogenesis of adaptation to hypoxia and HAPE occurrence. The expected results will benefit for the improvement of high altitude hypoxia adaptation epigenetic regulation related genes, and provide the basis for the further study of hypoxia.