Hospital of Chengdu Office of People's Government of Tibetan Autonomous Region (Hospital C.T.).
School of Basic Medical Sciences, Tibet University.
Genes Genet Syst. 2022 Jul 16;97(2):55-66. doi: 10.1266/ggs.21-00006. Epub 2022 May 28.
The prevalence of iron overload in Tibetans in Tibet is higher than that in Han. DNA methylation (DNAm) is closely related to iron metabolism and iron level. Nevertheless, the epigenetic status of Tibetans with iron overload is unknown, and we therefore aimed to explore whether the phenomenon observed in the Tibetan population is regulated by epigenetics. The results showed that 2.26% of cytosine was methylated in the whole genome, and that the rate of CG cytosine methylation was higher in individuals in the iron overload (TH) group than in those in the iron normal (TL) group. We analyzed differentially methylated genes (DMGs) in whole-genome bisulfite sequencing data from the TH and TL groups of high-altitude Tibetans. Protein-protein interaction and pathway analyses of candidate DMGs related to iron uptake and transport showed that epigenetic changes in 10 candidate genes (ACO1, CYBRD1, FLVCR1, HFE, HMOX2, IREB2, NEDD8, SLC11A2, SLC40A1 and TFRC) are likely to relate to iron overload. This work reveals, for the first time, changes of DNAm in Tibetan people with iron overload, which suggest that DNAm is a mechanism underlying differences in iron content between individuals in the high-altitude Tibetan population. Our findings should contribute to the study of iron metabolism and the overall health status of Tibetans.
西藏藏族人群铁过载的患病率高于汉族。DNA 甲基化（DNAm）与铁代谢和铁水平密切相关。然而，铁过载藏族人群的表观遗传状态尚不清楚，因此我们旨在探索在藏族人群中观察到的现象是否受表观遗传调控。结果表明，全基因组中有 2.26%的胞嘧啶发生甲基化，铁过载（TH）组个体中 CG 胞嘧啶甲基化率高于铁正常（TL）组。我们分析了来自高海拔藏族人群 TH 和 TL 组的全基因组亚硫酸氢盐测序数据中的差异甲基化基因（DMGs）。与铁摄取和转运相关的候选 DMGs 的蛋白质-蛋白质相互作用和途径分析表明，10 个候选基因（ACO1、CYBRD1、FLVCR1、HFE、HMOX2、IREB2、NEDD8、SLC11A2、SLC40A1 和 TFRC）的表观遗传变化可能与铁过载有关。这项工作首次揭示了铁过载藏族人群中 DNAm 的变化，表明 DNAm 是高海拔藏族人群个体铁含量差异的一种机制。我们的发现应该有助于铁代谢和藏族人整体健康状况的研究。
