|
| Integrative transcriptomic and mendelian randomization analysis based on the theory of similar diseases and syndromes of damp-turbidity-phlegm-rheum to identify core genes associated with heart failure risk in individuals with phlegm-damp constitution |
| Hits 480 Download times 230 Received:April 22, 2025 |
| View Full Text View/Add Comment Download reader |
| DOI
10.11656/j.issn.1673-9043.2025.08.01 |
| Key Words
similar diseases and syndromes of damp-turbidity-phlegm-rheum;phlegm-damp constitution;heart failure;mendelian randomization |
| Author Name | Affiliation | E-mail | | GUO Junchi | Tianjin University of Traditional Chinese Medicine, Graduate School, Tianjin 301617, China | | | ZHANG Mingyan | Tianjin University of Traditional Chinese Medicine, School of Traditional Chinese Medicine, Tianjin 301617, China | | | XU Qiang | Second Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Department of Cardiology, Tianjin 300250, China | | | LU Meijuan | Second Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Department of Cardiology, Tianjin 300250, China | lmj830127@163.com |
|
| Abstract
|
| [Objective] Phlegm-damp constitution is one of the classical constitutional types in Traditional Chinese Medicine（TCM），closely associated with metabolic disorders. According to the theory of Similar Diseases and Syndromes of Damp-turbidity-phlegm-rheum proposed by the National Master of TCM，Professor Zhang Boli，the phlegm-damp constitution is considered a key susceptibility factor for chronic diseases such as heart failure. However，the genetic mechanisms linking phlegm-damp constitution and heart failure remain largely unexplored. [Methods] Guided by the aforementioned TCM theory，this study employed “obesity” and “hyperlipidemia” as representative phenotypes of phlegm-damp constitution. Genome-wide association study（GWAS） data were integrated with protein quantitative trait loci（cis-pQTL） information to perform Mendelian randomization（MR） analysis，identifying core genes associated with phlegm-damp constitution. A gene model for heart failure risk in phlegm-damp individuals was constructed，followed by validation using transcriptomic sequencing data to assess differential gene expression. [Results] A total of 18 core genes were identified as being associated with both phlegm-damp constitution and heart failure risk. Among them， CPQ （Carboxypeptidase Q）， F2R （Coagulation Factor II Receptor，also known as PAR1），and ITGAL（Integrin Subunit Alpha L） showed significantly upregulated expression in heart failure tissues and were consistent in direction with MR results，indicating high robustness and interpretability. [Conclusion] This study establishes a genetic association model between phlegm-damp constitution and heart failure risk，offering a novel approach for the modernization and quantification of TCM constitution theory. It also provides potential genetic targets for early detection and precision intervention in heart failure. |
|
