Zhaxi Quzong, Gesang Luobu, Huang Ju, Suona Yangzong, Ci Bai, Danzeng Zhuoga, Zhang Rui, Liu Binyun
Institute of High Altitude Medicine, Tibet Autonomous Region People's Hospital, 18 Linkuo North Road, Chengguan District, Lhasa, Tibet Autonomous Region, People's Republic of China.
Biochem Genet. 2024 May 24. doi: 10.1007/s10528-024-10798-2.
Although the expression of many genes is associated with adaptation to high-altitude hypoxic environments, the role of epigenetics in the response to this harsh environmental stress is currently unclear. We explored whether abnormal DNA promoter methylation levels of six genes, namely, ABCA1, SOD2, AKT1, VEGFR2, TGF-β, and BMPR2, affect the occurrence and development of high-altitude polycythemia (HAPC) in Tibetans. The methylation levels of HAPC and the control group of 130 Tibetans from very high altitudes (> 4500 m) were examined using quantitative methylation-specific real-time PCR (QMSP). Depending on the type of data, the Pearson chi-square test, Wilcoxon rank-sum test, and Fisher exact test were used to assess the differences between the two groups. The correlation between the methylation levels of each gene and the hemoglobin content was explored using a linear mixed model. Our experiment revealed that the methylation levels of the TGF-β and BMPR2 genes differed significantly in the two groups (p < 0.05) and linear mixed model analysis showed that the correlation between the hemoglobin and methylation of ABCA1, TGF-β, and BMPR2 was statistically significant (p < 0.05). Our study suggests that levels of TGF-β and BMPR2 methylation are associated with the occurrence of HAPC in extreme-altitude Tibetan populations among 6 selected genes. Epigenetics may be involved in the pathogenesis of HAPC, and future experiments could combine gene and protein levels to verify the diagnostic value of TGF-β and BMPR2 methylation levels in HAPC.
尽管许多基因的表达与适应高海拔低氧环境有关，但表观遗传学在应对这种恶劣环境压力中的作用目前尚不清楚。我们探讨了ABCA1、SOD2、AKT1、VEGFR2、TGF-β和BMPR2这六个基因的DNA启动子甲基化水平异常是否会影响藏族人群高原红细胞增多症（HAPC）的发生和发展。使用定量甲基化特异性实时PCR（QMSP）检测了来自极高海拔（>4500米）的130名藏族HAPC患者和对照组的甲基化水平。根据数据类型，使用Pearson卡方检验、Wilcoxon秩和检验和Fisher精确检验来评估两组之间的差异。使用线性混合模型探讨每个基因甲基化水平与血红蛋白含量之间的相关性。我们的实验表明，两组中TGF-β和BMPR2基因的甲基化水平存在显著差异（p<0.05），线性混合模型分析表明，ABCA1、TGF-β和BMPR2的血红蛋白与甲基化之间的相关性具有统计学意义（p<0.05）。我们的研究表明，在6个选定基因中，TGF-β和BMPR2甲基化水平与极端海拔藏族人群中HAPC的发生有关。表观遗传学可能参与了HAPC的发病机制，未来的实验可以结合基因和蛋白质水平来验证TGF-β和BMPR2甲基化水平在HAPC中的诊断价值。
