Methylation Analysis Of Whole Genome DNA In High Altitude Pulmonary Edema And Bioinformatics Analysis Of Its Functions

With the smooth implementation of Chinese Western Development strategy,and the rapid economic development of the Qinghai-Tibet Plateau and the urgent demand in the national defense construction,there will be an increasing need that people who have lived in long-term low-altitude environment have to move to the plateau region to work.For the study of pathogenesis of High Altitude of Pulmonary Edema(HAPE),the exploration of predication of HAPE genetic maker,it has been a hot topic to prevent the occurrence of HAPE and to reduce the incidence of HAPE.Nevertheless,the epigenetics research of HAPE has not been completely carried out.In the current case-control study,the methylation regions were detected by Illumina 450K Infinium Methylation BeadChip,the functional annotation and pathway analysis for the screened out gene including the differentially methylated region were performed using the bioinformatical methods such as Gene Ontology(GO)and the Kyoto Genome and Genome Encyclopedia(KEGG)network resource.The results showed that for HAPE vs Sherpa:we found 36362 differential methylation regions involving 10856 genes.GO analysis listed 146 differential functional category entries and KEGG pathway analysis showed four differential methylation gene pathway;For HAPE vs normal control:we found 26564 differential methylation regions,involving 8977 genes.GO analysis listed 113 differential functional category entries and KEGG pathway analysis also showed four differential methylation gene pathway;For Sherpa vs normal group:we found 5280 differential methylation regions involving 2755 genes.GO analysis listed 37 functional category entries and KEGG pathway analysis showed only 1 differential methylation pathway.Functional annotation and classification of the KEGG pathway showed that the functions of the differential genes included GTP enzyme activity regulation,immune system process,protein binding,signal transduction regulation,cell communication regulation and other categories.In conclusion,the existed differentially methylated gene in HAPE patients may be one of the reasons for the occurrence and development of HAPE.The occurrence and development of HAPE is not the result of one or several signal pathways effect,but a multi-signal pathways working together through network structure and regulated by DNA methylation.All the studies indicates that the occurrence of HAPE is a result of a multi-signal pathways working together,Which may provide a reference for the further study of the molecular biological mechanism of HAPE.