Key Laboratory of Molecular Mechanism and Intervention Research for Plateau Diseases of Tibet Autonomous Region, School of Medicine, Xizang Minzu University, Xianyang, Shaanxi 712082, China; School of Basic Medical Sciences, Xizang Minzu University, Xianyang, Shaanxi 712082, China; Engineering Research Center of Tibetan Medicine Detection Technology, Ministry of Education, China.
School of Basic Medical Sciences, Xizang Minzu University, Xianyang, Shaanxi 712082, China.
Gene. 2022 Aug 5;834:146590. doi: 10.1016/j.gene.2022.146590. Epub 2022 May 25.
High altitude pulmonary edema (HAPE) is a fatal disease of fluid accumulation in the lungs resulting from acute exposure to high altitude and hypoxia. Now research has found that changes in DNA methylation are genetically related. We investigated the effects of hypermethylation and hypomethylation on HAPE.
We conducted an analysis of methylation in Chinese HAPE patients (53 patients and 53 controls). EpiTYPER of the Sequenom MassARRAY platform was used to detect DNA methylation at 43 CpG sites in CYP2S1.
We used probability analysis to find that only five CPG sites were not methylated. CYP2S1_1_CpG_11, CYP2S1_2_CpG_11, CYP2S1_2_CpG_12, CYP2S1_2_CpG_13, and CYP2S1_3_CPG_11.12 in the case group were lower than those in the control group. Our results showed that, 12 CpG sites had different methylation levels in HAPE patients compared with healthy controls, and only CYP2S1_1_CPG_1.2.3 (OR = 2.920, 95 %Cl = 1.228-6.946, p = 0.015) had a higher risk of hypermethylation than hypomethylation. ROC curve analysis showed that the methylation level of CYP2S1 could effectively predict the risk of HAPE patients.
Our results showed that several CpG sites in the promoter regions of CYP2S1 gene were abnormally methylated in HAPE patients.
高原肺水肿（HAPE）是一种由于急性暴露于高海拔和缺氧导致肺部液体积累的致命疾病。现在的研究发现，DNA 甲基化的变化与遗传有关。我们研究了高甲基化和低甲基化对 HAPE 的影响。
我们对中国 HAPE 患者（53 例患者和 53 例对照）进行了甲基化分析。EpiTYPER 测序平台用于检测 CYP2S1 中 43 个 CpG 位点的 DNA 甲基化。
我们使用概率分析发现只有 5 个 CpG 位点没有甲基化。病例组中 CYP2S1_1_CpG_11、CYP2S1_2_CpG_11、CYP2S1_2_CpG_12、CYP2S1_2_CpG_13 和 CYP2S1_3_CPG_11.12 的甲基化水平低于对照组。我们的结果表明，与健康对照组相比，HAPE 患者有 12 个 CpG 位点的甲基化水平不同，只有 CYP2S1_1_CPG_1.2.3（OR=2.920，95%Cl=1.228-6.946，p=0.015）的高甲基化比低甲基化风险更高。ROC 曲线分析表明，CYP2S1 的甲基化水平可以有效预测 HAPE 患者的风险。
我们的结果表明，CYP2S1 基因启动子区域的几个 CpG 位点在 HAPE 患者中异常甲基化。
