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Abstract

Background

Accumulating evidence has shown the association between DNA methylation and hydroxymethylation and the development of atherosclerosis. However, little is known about the diagnostic value of DNA methylation and hydroxymethylation for coronary atherosclerosis. Carotid plaque has a significant correlation with coronary atherosclerosis, which is a common marker for coronary atherosclerosis.

Purpose

The major aim of the present study is to determine whether DNA methylation and hydroxymethylation combined with carotid plaques can be useful to the diagnosis of coronary atherosclerosis.

Methods

113 patients undergoing carotid ultrasound were enrolled into the study and measured the levels of 5-methylcytosine (5-mC) and 5-hydroxymethylcytosine (5-hmC). Crouse score and Gensini score were used to evaluate the severity of carotid and coronary atherosclerosis, respectively.

Results

With the increasing of severity of carotid plaque and Crouse score, a stepwise upward trend was observed in 5-mC and 5-hmC levels, which were significantly correlated with the risk factors such as FPG and HbA1c levels, Crouse score and Gensini score. Crouse score and 5-hmC, not 5-mC, were the risk factors for coronary atherosclerosis after adjustment for the risk factors. Receiver operating characteristic (ROC) analysis for comparing their diagnostic value for coronary atherosclerosis indicated that 5-hmC combined with Crouse score was the diagnostic biomarker for coronary atherosclerosis, with the highest areas under the curve (AUC), valuable sensitivity and specificity.

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Logistic regression analysis

VariablesUnivariate analysisMultivariate analysis
OR (95% CI)POR (95% CI)P
History of DM3.680 (1.645–8.235)0.0024.487 (0.227–88.680)0.324
FPG (mmol/L)1.782 (1.219–2.605)0.0030.972 (0.307–3.071)0.961
HbA1c (%)1.785 (1.191–2.674)0.0052.861 (0.717–11.422)0.137
TC (mmol/L)1.171 (0.913–1.502)0.214
LDL-c (mmol/L)1.383 (0.939–2.036)0.100
hs-CRP (mg/L)1.099 (1.020–1.184)0.0141.268 (1.013–1.588)0.038
Crouse score1.795 (1.445–2.230)<0.0011.863 (1.053–3.297)0.033
5-mC (%)3.221 (1.851–5.604)<0.0010.983 (0.386–2.505)0.972
5-hmC (%) per 0.01%1.484 (1.265–1.741)<0.0011.767 (1.250–2.499)0.001
VariablesUnivariate analysisMultivariate analysis
OR (95% CI)POR (95% CI)P
History of DM3.680 (1.645–8.235)0.0024.487 (0.227–88.680)0.324
FPG (mmol/L)1.782 (1.219–2.605)0.0030.972 (0.307–3.071)0.961
HbA1c (%)1.785 (1.191–2.674)0.0052.861 (0.717–11.422)0.137
TC (mmol/L)1.171 (0.913–1.502)0.214
LDL-c (mmol/L)1.383 (0.939–2.036)0.100
hs-CRP (mg/L)1.099 (1.020–1.184)0.0141.268 (1.013–1.588)0.038
Crouse score1.795 (1.445–2.230)<0.0011.863 (1.053–3.297)0.033
5-mC (%)3.221 (1.851–5.604)<0.0010.983 (0.386–2.505)0.972
5-hmC (%) per 0.01%1.484 (1.265–1.741)<0.0011.767 (1.250–2.499)0.001
Open in new tab

Logistic regression analysis

VariablesUnivariate analysisMultivariate analysis
OR (95% CI)POR (95% CI)P
History of DM3.680 (1.645–8.235)0.0024.487 (0.227–88.680)0.324
FPG (mmol/L)1.782 (1.219–2.605)0.0030.972 (0.307–3.071)0.961
HbA1c (%)1.785 (1.191–2.674)0.0052.861 (0.717–11.422)0.137
TC (mmol/L)1.171 (0.913–1.502)0.214
LDL-c (mmol/L)1.383 (0.939–2.036)0.100
hs-CRP (mg/L)1.099 (1.020–1.184)0.0141.268 (1.013–1.588)0.038
Crouse score1.795 (1.445–2.230)<0.0011.863 (1.053–3.297)0.033
5-mC (%)3.221 (1.851–5.604)<0.0010.983 (0.386–2.505)0.972
5-hmC (%) per 0.01%1.484 (1.265–1.741)<0.0011.767 (1.250–2.499)0.001
VariablesUnivariate analysisMultivariate analysis
OR (95% CI)POR (95% CI)P
History of DM3.680 (1.645–8.235)0.0024.487 (0.227–88.680)0.324
FPG (mmol/L)1.782 (1.219–2.605)0.0030.972 (0.307–3.071)0.961
HbA1c (%)1.785 (1.191–2.674)0.0052.861 (0.717–11.422)0.137
TC (mmol/L)1.171 (0.913–1.502)0.214
LDL-c (mmol/L)1.383 (0.939–2.036)0.100
hs-CRP (mg/L)1.099 (1.020–1.184)0.0141.268 (1.013–1.588)0.038
Crouse score1.795 (1.445–2.230)<0.0011.863 (1.053–3.297)0.033
5-mC (%)3.221 (1.851–5.604)<0.0010.983 (0.386–2.505)0.972
5-hmC (%) per 0.01%1.484 (1.265–1.741)<0.0011.767 (1.250–2.499)0.001

graphic
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Conclusions

These findings suggest 5-hmC level combined with Crouse score may provide the meaningful information for coronary atherosclerosis diagnosis.

Acknowledgement/Funding

National Natural Science Foundation of China (No.81570212, No.31800976)

Coronary Artery Disease: Noninvasive Diagnostic Methods
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Tuesday 3 September 2019
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