Abstract
Background
The Xueyu Zheng (XYZ) phenome is central to coronary heart disease (CHD), but efforts to detect genetic associations in the XYZ phenome have been disappointing.
Methods
The phenomic alteration-related genes (PARGs) for the XYZ phenome were screened using |ρ| > 0.4 and p < 0.05 after treatment with Danhong injection at day 14 and day 30. Then, the driver genes for the Protein-Protein Interaction (PPI) networks of the PARGs established using STRING 11.0 were detected using a personalized network control algorithm (PNC). Finally, the molecular correlations of the driver genes with the XYZ phenome were analyzed with the Gene Ontology (GO) biological processes and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways from a holistic viewpoint.
Results
A total of 525 and 309 PARGs in the XYZ phenome at day 14 and day 30 were identified. These genes were separately enriched in 48 and 35 pathways. Furthermore, five driver genes were detected. These genes were mainly correlated with endoplasmic reticulum stress-mediated apoptosis and autophagy regulation, which could suppress atherosclerosis progression.
Conclusion
Our study detected the drug-responsive PARGs of the XYZ phenome in CHD and provides an exemplary strategy to investigate the genetic associations among this common phenome and its component symptoms in patients with CHD.
Trial Registration
ClinicalTrials.gov, NCT01681316; registered on September 7, 2012.
Graphical Abstract
Abbreviations
XYZ, Xueyu Zheng; CHD, Coronary Heart Disease; PARGs, Phenomic Alteration-Related Genes; PPI, Protein–Protein Interaction; PNC, Personalized Network Control Algorithm; DHI, Danhong Injection; SAQ, Seattle Angina Questionnaire; CCA, Canonical Correlation Analysis; CCS, Canadian Cardiovascular Society; GO, Gene Ontology; KEGG, Kyoto Encyclopedia of Genes and Genomes; BMI, Body Mass Index; SD, Standard Deviation.
Data Sharing Statement
The data that support the findings of this study have been deposited in the CNSA (https://db.cngb.org/cnsa/) of CNGBdb with accession number CNP0000461.
Ethics Approval and Consent to Participate
The trial protocol was approved by the Central Institutional Review Committee of the Chinese People’s Liberation Army General Hospital (IRB no. [2012] Yao (025)).
This study is a multicenter study, the samples were collected in the Chinese PLA General Hospital (301 Hospital) and Xuanwu Hospital Capital Medical University, so the ethical affiliations is the Chinese PLA General Hospital (301 Hospital).
Consent for Publication
All data generated or analyzed during this study are included in this published article.
Acknowledgments
We thank all the staff of the 31 clinical centers for their contributions to the investigation of the trial, especially the samples collectors from Chinese PLA General Hospital (301 Hospital) and Xuanwu Hospital Capital Medical University. This work was funded by China Academy of Chinese Medical Sciences (CACMS) Innovation Fund (CI2021A05033), China National Science and Technology Major Project for “Significant New Drugs Development” (2011ZX09304-07), National Natural Science Foundation of China (81673833) and China Fundamental Research Funds for the Central Public Welfare Research Institutes (ZZ0908029, z0647, z0747). Graphical abstract and figure 9 created with BioRender.com.
Disclosure
The authors declare no competing interests.