The Reversion of DNA Methylation at Coronary Heart Disease Risk Loci in Response to Prevention Therapy

Abstract

Coronary heart disease (CHD) is preventable, but the methods for assessing risk and monitoring response rely on imprecise lipid-based assessments. Recently, we have shown that an integrated genetic–epigenetic test that includes three methylation-sensitive digital PCR assays predicts 3-year risk for incident CHD better than lipid-based methods. However, whether methylation sites change in response to therapies that alter CHD risk is not known. Therefore, we assessed methylation at these three incident CHD-related sites in DNA from 39 subjects before and after three months of biochemically verified smoking cessation, then analyzed the relationship between change in methylation at each of the sites to the change in smoking intensity as assessed by cg05575921 methylation. We found that, in those who quit smoking, methylation change at one CHD risk marker (cg00300879) was significantly associated with change in cg05575921 methylation (p < 0.04). We conclude that changes in incident CHD-related methylation occur within three months of cessation of smoking, a major risk factor for CHD. This suggests that the effectiveness of treatment of other CHD risk factors, such as high cholesterol, may be similarly quantifiable using epigenetic approaches. Further studies to determine the relationship of changes of methylation status in response to treatment of other CHD risk factors are indicated.

The Reversion of the Epigenetic Signature of Coronary Heart Disease in Response to Smoking Cessation

“…Previously, we have shown that one of the three MSdPCR measures contained in an integrated genetic–epigenetic test for assessing the 3-year risk for CHD significantly changed as a function of treatment for smoking [ 10 ]. Since smoking is a key driver of CHD [ 11 , 12 ] and smoking cessation therapy can markedly improve survival in smokers with CHD, this suggests that methylation at one of more of the six loci assessed in the PrecisionCHD test may also respond to smoking therapy.…”

Heat selection enables highly scalable methylome profiling in cell-free DNA for noninvasive monitoring of cancer patients

“…Nonetheless, there is substantial upfront and operational cost for designing, synthesizing, validating, and using these capture probes. Commercial hybridization capture kits of comparable coverage cost >$200 ( 4 ), setting a minimum cost for performing these assays. Furthermore, once a panel is designed, it is inflexible to be applied to other types of diseases or subtypes that have a different set of differentially methylated regions (DMRs).…”