| Object: Atherosclerosis (Atherosclerosis, AS) is a serious and commondisease participated by multiple genetic and environmental factors. AS involved inchronic complicated diseases, cardio-cerebral vascular diseases that is a seriousdanger to human health and frequently-occurring disease, morbidity and mortalityrates of various diseases. But early molecular diagnostic markers and methods ofAS have not been fully elucidated. DNA methylation is the unique commonmodification in DNA, which mainly regulates gene expression in transcriptionlevel, also is a link that contact genetic and environment factors. And DNAmethylation occurs earlier than the clinical symptoms of disease, therefore, DNAmethylation is thought to be an early diagnostic marker of biology AS. AS is amultiple factor and complex diseases, in the past research only confined to a singleor a few genes methylation, the judgment of AS relying on the methylation statusof a single or a few genes is not accurate, therefore, for early detection of AS, weinvestigated DNA methylation profile of AS patients and matched controls inperipheral blood in order to establish a biomarker panel potentially useful forearly detection of AS, finding an effective method from gene profile for AS earlydiagnosis has an important role in improving the level and quality of people’s life.Methods and results: AS patients and matched controls (50and50) wererecruited for peripheral blood DNA methylation analyses at the12genes promoterloci using nested methylation specific PCR (ntMSP) in a test set. Based on the testset we determined the promoter methylation of TIMP-1, ABCA1, and ACAT1ascandidate biomarkers with the best sensitivity of88%and specificity of90%. Inan independent validation set (n=100) we validated the candidate biomarkers for further use in early AS detection. In the validation set combined TIMP-1, ABCA1,and ACAT1methylation achieved sensitivity of88%and a specificity of70%, withcoincidence rate of79%, respectively. Conclusions: In this first pilot study, DNAmethylation patterns change significantly in AS patients and AS-related genes inperipheral blood cells. AS-specific methylation of the three-gene panel (TIMP-1,ABCA1, and ACAT1) might be a valuable biomarker for the early detection of AS.Conclusion: The results demonstrate that related gene DNA methylationchange in AS are frequently event. The DNA methylation of ACAT1and PPARα inperipheral blood of AS patients were significantly lower than in the matchedcontrols, while the DNA methylation of TIMP-1, ABCA1,5-LO significantlyhigher than in the matched controls. The special DNA methylation profile ofTIMP-1, ACAT1and ABCA1is a hope and effective method in diagnostic AS witha sensitivity of70%, specificity of88%. |
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