The Exploration About Forensic Diagnosis Of Drug Allergic Sudden Death Base On DNA Methylation

Objective:Forensic diagnosis of drug allergic sudden death is a hard problem in forensic pathology.It need forensic pathologists to solve that finding accurate and objective laboratory diagnostic indicators.Through research and analysis of DNA methylation differences between drug allergic deaths and normal people,this study try to find some differential methylation sites of drug allergy and provide accurate and objective laboratory diagnostic indicators for forensic identification of drug allergic sudden death.Methods:1.Blood samples were collected from normal people(6 cases)and drug-allergic sudden death(18 cases).The DNA methylation of whole blood were tested by Illumina Methylation EPIC chips.2.Chips data analysis: The methylation difference analysis,genes annotation and genes association study were achieved by ChAMP packages from R language;The GO and KEGG function enrichment analysis were achieved by R-topGO and R-KOBAS packages from R language.3.The functions of DNA methylation sites/regions associated with drug allergic sudden death were analyzed based on the results of genes association study,GO and KEGG.4.Some DNA methylation indicators of drug allergic sudden death were screened based on the results of DMP,DMR and genes association study.Results:1.The drug allergic sudden death is significantly associated DNA methylation of HLADMA,HLA-DMB,HLA-DOB,HLA-DPA1,and HLA-DPB1 genes.2.Cephalosporin allergic sudden death is related to the CCL5 gene regions of promoter hypo-methylated and HLA-DOB genes methylation.3.What genes DNA methylation are differential on the way of ‘Chemokine ? PI3K-Art ? protein kinase' were observed of Cephalosporin allergic sudden death.This study screened some CpG sites and CpG islands that methylation levels stable in normal people and significant different in drug allergic sudden death.Conclusion:It is associated between drug allergies with DNA methylation.And allergies caused by different drugs may cause DNA methylation differences in different regions.It is feasible that the drug allergic sudden death diagnosed base on DNA methylation difference in Forensic.Drug allergies could be prevented and treated by regulating DNA methylation in clinical.