Differentially Expressed Genes In Psoriasis And Their CpG Islands Methylation Analysis

OBJECTIVE Psoriasis(PS)is a common polygenic hereditary skin disease,which is caused by the interaction of environmental and genetic factors.It is no longer considered that the damage is limited to the skin,but may affect the whole system.Epidemiological studies show that psoriasis patients are more likely to get some diseases than diabetes,such as diabetes,liver abnormalities and anxiety disorders.The incidence rate of psoriasis is increasing year by year in recent years.The etiology and pathogenesis of psoriasis have been a hot topic and difficult point in our department of dermatology research.In this study,the technology of Illumina Infinium methylation epic beadchip(DNA methylation 850 k chip)and the analysis method of mRNA human transcriptome sequencing(mRNA SEQ)were used for the first time to jointly analyze the DNA methylation and mRNA transcription of whole genome Cp G island in the skin tissues of skin lesions and non skin lesions of patients with psoriasis,and to deeply explore the pathogenesis of psoriasis from the aspects of epigenetics,And then explore the new theoretical basis and therapeutic targets of the disease.METHODS Five patients with psoriasis treated in the people’s Hospital of Inner Mongolia Autonomous Region were collected.The skin tissues of skin lesions and non skin lesions were taken,and the tissue DNA and total RNA were extracted.The whole genome DNA methylation sequencing and expression quantitative analysis were carried out by 850 k chip and mRNA human transcriptome sequencing technology respectively.Finally,the results of DNA methylation sequencing and mRNA experiment were combined to find the common differentially expressed genes,and the function and pathway enrichment of these genes were analyzed.RESULTS We derived a sufficiently comprehensive genome-wide DNA methylation map and co differentially expressed genes,and screened a large number of hypermethylated and lowly expressed genes and hypomethylated and highly expressed genes.The specific results were as follows:(1)compared with normal nonlesional skin tissues,whole genome DNA from psoriatic lesional skin samples exhibited aberrant methylation status,with aberrant changes occurring in 54613 differentially methylated sites(1963 Cp G islands)and 322 differentially methylated regions(83 Cp G islands).Of these,17591 were hypermethylated(695 Cp G islands)and 37022 were hypomethylated(1268 Cp G islands).(2)The number of genes that were co differentially expressed was 1183,of which 659 were up-regulated(55.7%)and 524 were down regulated(44.29%).(3)A total of 426 genes were associated with both the hypermethylated and the differentially expressed mRNAs after joint analysis of the data from the aberrant methylation of Cp G islands in the lesional and nonlesional skin samples of psoriasis patients,including 183 genes showing hypermethylation and low expression and 243 genes showing hypomethylation and high expression,respectively.(4)Among these 184 hypermethylated and lowly expressed genes,13 genes including aatk,BMP4,and BRSK2 had methylation sites located in Cp G islands(7%),and among 244 genes with hypomethylated and highly expressed genes,13 genes including AXIN1,cep131,and fam83 h had methylation sites located in Cp G islands(5%).(5)There is a negative correlation between the degree of DNA aberrant methylation of Cp G islands and their expression levels in lesional skin of psoriasis patients compared with nonlesional skin tissue.(6)Either the hypermethylated and lowly expressed genes or the hypomethylated and highly expressed genes were significantly different in terms of their go functions and enriched pathway KEGG,and all were significantly associated with the occurrence and development of psoriasis.CONCLUSION Through the analysis of the above gene results,we get the following summary:(1)The genomic DNA of skin lesions in patients with psoriasis showed abnormal methylation compared with the skin of normal non skin lesions.(2)There are more differentially expressed mRNA in the genomic DNA in the skin lesions of patients with psoriasis compared with the skin tissues of non lesions.(3)Psoriasis is not caused by a single gene mutation,but a polygenic genetic disease,which is caused by the interaction and interaction of multiple genes.(4)There was a negative correlation between the abnormal methylation degree of Cp G island DNA and its expression level in skin lesions and non skin lesions of patients with psoriasis.(5)There was a negative correlation between the abnormal methylation degree of Cp G island DNA and its expression level in the skin tissue of psoriasis patients.(6)The differentially expressed genes at methylation level are related to pathophysiological processes.Their functions involve many aspects,and their signal pathways are complex.Among them,c AMP signaling pathway and drug metabolism-other enzymes pathway have strong correlation with the occurrence and development of psoriasis.