DNA methylation composition related to death risk of coronary heart disease patients and screening method and application thereof

A methylation and coronary heart disease technology, applied in the field of epigenetics, can solve problems such as reducing gene expression levels, and achieve the effects of reducing model dimensions, reducing costs, and improving accuracy

Active Publication Date: 2020-10-30
GUANGDONG GENERAL HOSPITAL
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  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

DNA methylation inhibits the transcription of genes by altering the chromatin structure and inhibiting the binding of transcription factors and cofactors to the corresponding target sites, thereby reducing the expression level of genes

Method used

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  • DNA methylation composition related to death risk of coronary heart disease patients and screening method and application thereof
  • DNA methylation composition related to death risk of coronary heart disease patients and screening method and application thereof
  • DNA methylation composition related to death risk of coronary heart disease patients and screening method and application thereof

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Experimental program
Comparison scheme
Effect test

Embodiment 1

[0038] This embodiment provides a method for screening methylation sites for prognosis diagnosis of coronary heart disease, including the following steps (flow process as follows: figure 1 shown):

[0039] (1) Data of patients with coronary heart disease

[0040] The selected subjects were patients with stable coronary heart disease and non-acute ACS coronary heart disease diagnosed by Guangdong Provincial People's Hospital who received PCI treatment. This protocol was approved by the Ethics Committee of Guangdong Provincial People's Hospital, and each subject signed an informed consent. The cases were collected from January 2010 to December 2013.

[0041] (2) Clinical endpoints and follow-up plan of the study

[0042] The clinical endpoint of this study was death. After the patients are selected, they will be followed up regularly by telephone every 6 months, and they will be asked in detail and recorded whether the patients have adverse cardiovascular events and so on. T...

Embodiment 2

[0063] Example 2 Test data set to evaluate model prediction effect

[0064] The AUC (area under the curve) of the time-dependent ROC curve (Receiver Operating Characteristic curve, receiver operating curve) is used to evaluate the predictive effect of the model constructed in Example 1, and the results are as follows image 3 .

[0065] The value range of AUC is between 0-1, and the larger the AUC, the better the prediction effect of the model. like image 3 , LassoCox regression model AUC in the training set 1年 =0.869, AUC 3年 =0.902, AUC 5年 = 0.879, AUC in the test set 1年 =0.706, AUC 3年 =0.767, AUC 5年 =0.928, indicating that the model predicts the prognosis of patients better.

Embodiment 3

[0066] Example 3 Centrally evaluate the prediction effect of the model through the test data

[0067] According to the M value of these 16 methylation sites and the regression coefficient in the Lasso Cox model, the methylation risk score of the test set samples can be obtained. Whether in the training data set or the test data set, the methylation risk score can well predict the prognosis of patients with coronary heart disease. The MRS of patients with death events is significantly higher than that of patients without events (p Figure 4 . According to the median of the methylation risk score as the cut-off value (median of 5.598 in this example), the patients were divided into high risk group (MRS>5.598) and low risk group with roughly equal number of observations. Risk group (MRS≤5.598). The Kaplan-Meier survival curves of the two groups were drawn respectively, and the Log-rank test was used to test whether there was a significant difference in the survival period between t...

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Abstract

The invention provides a group of DNA methylation markers for evaluating survival prognosis risk of coronary heart disease. The marker comprises methylation sites corresponding to the following genes:chr3: 101901234, SEMA3B, CORO2B, SLC39A8, chr7: 27235733, chr10: 3086002, chr2: 164594200, RNASEH1, chr10: 13489731, ABCA3, ZNF444, UBE2E2, DAZAP1, NAT10, DDAH1 and FKBP5. Prognosis and death risks of coronary heart disease patients can be predicted by monitoring changes of methylation levels of the 16 sites. The invention also constructs a model for evaluating the survival prognosis risk of thecoronary heart disease based on the 16 methylation sites, and the accuracy of blood diagnosis and prognosis prediction of patients with the coronary heart disease can be improved through the model. According to the method, the Lasso Cox regression model is used for screening important variables, so that the model dimension is greatly reduced, the detection cost is favorably reduced, and the popularization in clinical application is facilitated.

Description

technical field [0001] The invention belongs to the technical field of epigenetics, and relates to a DNA methylation composition related to the death risk of coronary heart disease patients, a screening method and application thereof. Background technique [0002] Coronary heart disease, also known as coronary atherosclerotic (AS) heart disease, is a kind of heart disease caused by atherosclerotic lesions in coronary arteries that cause stenosis or blockage of the vessel lumen, resulting in myocardial ischemia, hypoxia or necrosis. sick. Coronary heart disease is one of the diseases with high morbidity and mortality in the world, and its incidence is gradually increasing. According to the Lancet public data, ischemic heart disease has been the second leading cause of death in the Chinese population in the past ten years, and its pathological process is characterized by progressive and irreversible characteristics. to bear. At present, the methods for predicting the risk o...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C12Q1/6883C12N15/11G06F17/18G16B5/00G16B20/30G16B20/40
CPCC12Q1/6883G16B20/30G16B20/40G16B5/00G06F17/18C12Q2600/154C12Q2600/118
Inventor 钟诗龙陈慧秦敏
Owner GUANGDONG GENERAL HOSPITAL
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