Genome-Wide Analysis Of DNA Methylation And Acute Cerebral Infarction And Bioinformatics Analysis Of The Functions

Purpose: Cerebral infarction is a leading public health issue worldwide.Genetic factors play a crucial role in the development of IS.However,whether epigenetic modification contributes to the pathogenesis of this disease has not been systematically investigated.(1)In this study,the DNA methylation levels in patients with acute cerebral infarction and healthy controls were analyzed by Illumina Infinium Human Methylation 450 K,and the significant changes in DNA methylation levels in patients with acute cerebral infarction were identified.Functional enrichment analysis was used to elucidate the role of DNA methylation in the development and progression of acute cerebral infarction.(2)the difference of methylation level in PTPRN2 gene between acute cerebral infarction and healthy controls were verified,which may provide new target and theoretical basis for early diagnosis and treatment of acute cerebral infarction.Methods:(1)In this study,12 patients with acute cerebral infarction and 12 healthy blood samples were collected.Illumina Infinium Human Methylation450 K were performed to examine genome-wide DNA methylation profiles.GO and KEGG analysis was used to enrich the functions of the differential genes.(2)94 patients with acute cerebral infarction and 77 healthy controls were collected.MassARRAY EpiTYPER DNA methylation analysis technique was used to analyze 8 CpG sites in PTPRN2 gene in these samples.Results:(1)Compared with the methylation level of the whole genome in the acute cerebral infarction group and the healthy control group,a total of 1014 methylation sites were screened for differences in methylation levels(p<0.01,mean value >0.05).(2)In the large sample validation phase,eight CpG sites of the PTPRN2 gene selected by the gene chip were analyzed by comparison between the case group and control group.and a total of 7 CpG site data(CpG2,CpG3,CpG4,CpG5,CpG6,CpG7,and CpG8)were obtained by MassARRAYanalysis technology.The experimental results showed that 7 CpG sites were all at high methylation levels.And it was found that the methylation levels of CpG4,CpG5,CpG6,and CpG8 were significantly between the experimental group and the control group(p=0.019;p=0.032;p=0.029;p=0.019).There was no significant in CpG2,CpG3,CpG7 sites between the case and control group(p>0.05).Conclusion:(1)The level of methylation in the whole genome was different between patients with acute cerebral infarction and the healthy control group.This may be one of the important epigenetic causes leading to the occurrence and development of acute cerebral infarction.(2)The methylation of PTPRN2 gene was significantly increased in patients with acute cerebral infarction,which might be an epigenetic biomarker.