Exploring the Causal Effects of Circulating ST2 and Galectin-3 on Heart Failure Risk: A Mendelian Randomization Study

Frontiers in Cardiovascular Medicine

article

Xizhi Wang¹  Xingchen Wang¹  Jun Zhu¹  Yu Liu²  Lenan Zhuang¹  Zhe Zhang¹  Danfeng Zhong¹  Wenbin Zhang¹  Dongwu Lai¹ 

[1] Key Laboratory of Cardiovascular Intervention and Regenerative Medicine of Zhejiang Province, Department of Cardiology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine;Department of Cardiac Surgery, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine

关键词: ST2;    galectin-3;    heart failure;    Mendelian randomization;    causal association;   

DOI  :  10.3389/fcvm.2022.868749

学科分类：地球科学(综合)

来源: Frontiers

【 摘 要 】

Background Heart failure (HF), primarily caused by conditions such as coronary heart disease or cardiomyopathy, is a global health problem with poor prognosis and heavy burden on healthcare systems. As biomarkers of myocardial injury and fibrosis, suppression of tumorigenicity 2 (ST2) and galectin-3 were recommended for prognosis stratification in HF guidelines. However, the causality between these two mediators and HF remains obscure. This study aimed to explore the causal relationship of genetically determined ST2 and galectin-3 with the risk of HF. Methods We used the two-sample Mendelian randomization (MR) method, incorporating available genome-wide association summary statistics, to investigate the causal association of ST2 and galectin-3 with HF risk. We applied inverse-variance weighted analysis as the main method of analysis. Results In our final MR analysis, 4 single-nucleotide polymorphisms (SNPs) of ST2 and galectin-3, respectively, were identified as valid instrumental variables. Fixed-effect inverse variance weighted (IVW) analysis indicated that genetically predicted ST2 and galectin-3 were not causally associated with HF risk 3. [odds ratio (OR) = 0.9999, 95% confidence interval [CI] = 0.9994–1.0004, p = 0.73; OR = 1.0002, 95% CI = 0.9994–1.0010, p = 0.60, respectively]. These findings were robust in sensitivity analyses, including MR-Egger regression and leave-one-out analysis. Conclusion This MR study provided no evidence for the causal effects of ST2 and galectin-3 on HF risk.

【 授权许可】

CC BY