Abstract: Objective To investigate the role of DNA methylation of EPAS1 gene in the adaptation to hypoxia at high altitude by comparing the difference of DNA methylation levels in the EPAS1 gene promoter region among Tibetan group,plain Han group and plateau Han group （>10 years）. Methods Blood samples were collected from 30 healthy male volunteers of Tibetan, plain Han and plateau Han,and genomic DNA was extracted. Agena Massarray nucleic acid mass spectrometry was used to quantitatively detect the difference in the degree of DNA methylation among these groups. Total RNA was extracted from the above groups,and the reverse transcription was cDNA. The mRNA expression levels of EPAS1 in different groups were detected by qRT-PCR. Results The overall DNA methylation degree of EPAS1 gene promoter region was 8.87%±10.31%,7.17%±10.12%,9.32%±13.07% in the plain Han,plateau Han and Tibetan,respectively,and there was no statistical difference among the three groups（P>0.05）. The methylation levels of part of CpG sites in EPAS1 gene promoter region were significantly different among the three groups（P<0.05）. At the same time,the relationship between sequence mutations at rs13419896,rs1868092 and rs4953354 of EPAS1 gene and DNA methylation was analyzed. There was no statistical difference among the groups（P>0.05）. The expression level of EPAS1 mRNA was significantly higher in plateau Han than in plain Han,and slightly higher in Tibetan than in plain Han. Conclusion The DNA methylation level of some CpG sites in EPAS1 gene promoter region is different between Tibetan and Han population,and plateau Han may participate in the adaptation process of hypoxia through the change of DNA methylation.

Key words: EPAS1 gene, DNA methylation, High altitude hypoxia