F2RL3 Methylation in the Peripheral Blood as a Potential Marker for the Detection of Coronary Heart Disease: A Case-Control Study

Zhao, Xiaojing; Zhu, Liya; Yin, Qiming; Xu, Zhenguo; Jia, Qi; Yang, Rongxi; He, Kunlun

doi:10.3389/fgene.2022.833923

Cited by 10 publications

(6 citation statements)

References 55 publications

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“…A total of 1452 CpG sites were mentioned once or more in at least two of the publications, 441 CpG sites were mentioned once or more in at least three publications, and two CpG sites were mentioned in ≥ 6 publications (Table 2 ). The two latter CpG sites are cg01656216 near gene ZNF438 (mentioned in [ 10 , 22 , 30 , 60 , 65 , 108 ]) and cg03636183 near gene F2RL3 (mentioned in [ 49 , 69 , 75 , 79 , 113 ], Table 3 ). These two CpG sites are also part of the methylation clocks.…”

Section: Resultsmentioning

confidence: 99%

“…Three out of six papers mentioning cg01656216 [ 22 , 30 , 108 ] have vascular disease as an outcome, whereas the three other publications had investigated epigenetic age [ 10 , 60 , 65 ]. In the case of cg03636183, three out of six publications had coronary heart disease or myocardial infarction as the outcome [ 75 , 79 , 113 ], and the other three had investigated smoking or air pollution [ 12 , 49 , 69 ].…”

Section: Resultsmentioning

confidence: 99%

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DNA methylation and cardiovascular disease in humans: a systematic review and database of known CpG methylation sites

et al. 2023

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Background Cardiovascular disease (CVD) is the leading cause of death worldwide and considered one of the most environmentally driven diseases. The role of DNA methylation in response to the individual exposure for the development and progression of CVD is still poorly understood and a synthesis of the evidence is lacking. Results A systematic review of articles examining measurements of DNA cytosine methylation in CVD was conducted in accordance with PRISMA (preferred reporting items for systematic reviews and meta-analyses) guidelines. The search yielded 5,563 articles from PubMed and CENTRAL databases. From 99 studies with a total of 87,827 individuals eligible for analysis, a database was created combining all CpG-, gene- and study-related information. It contains 74,580 unique CpG sites, of which 1452 CpG sites were mentioned in ≥ 2, and 441 CpG sites in ≥ 3 publications. Two sites were referenced in ≥ 6 publications: cg01656216 (near ZNF438) related to vascular disease and epigenetic age, and cg03636183 (near F2RL3) related to coronary heart disease, myocardial infarction, smoking and air pollution. Of 19,127 mapped genes, 5,807 were reported in ≥ 2 studies. Most frequently reported were TEAD1 (TEA Domain Transcription Factor 1) and PTPRN2 (Protein Tyrosine Phosphatase Receptor Type N2) in association with outcomes ranging from vascular to cardiac disease. Gene set enrichment analysis of 4,532 overlapping genes revealed enrichment for Gene Ontology molecular function “DNA-binding transcription activator activity” (q = 1.65 × 10–11) and biological processes “skeletal system development” (q = 1.89 × 10–23). Gene enrichment demonstrated that general CVD-related terms are shared, while “heart” and “vasculature” specific genes have more disease-specific terms as PR interval for “heart” or platelet distribution width for “vasculature.” STRING analysis revealed significant protein–protein interactions between the products of the differentially methylated genes (p = 0.003) suggesting that dysregulation of the protein interaction network could contribute to CVD. Overlaps with curated gene sets from the Molecular Signatures Database showed enrichment of genes in hemostasis (p = 2.9 × 10–6) and atherosclerosis (p = 4.9 × 10–4). Conclusion This review highlights the current state of knowledge on significant relationship between DNA methylation and CVD in humans. An open-access database has been compiled of reported CpG methylation sites, genes and pathways that may play an important role in this relationship.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

DNA methylation and cardiovascular disease in humans: a systematic review and database of known CpG methylation sites

et al. 2023

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“…This investigation is based on a case–control study, details of which have been reported elsewhere [ 37 ]. Briefly, 180 patients with CHD and 184 controls were collected from the Chinese PLA General Hospital from 2018 to 2019.…”

Section: Methodsmentioning

confidence: 99%

The association between DNA methylation of 6p21.33 and AHRR in blood and coronary heart disease in Chinese population

Zhu

Yang

et al. 2022

BMC Cardiovasc Disord

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Background Early detection could significantly improve the prognosis of coronary heart disease (CHD). In-invitro diagnostic technique may provide a solution when sufficient biomarkers could be identified. Pertinent associations between blood-based aberrant DNA methylation and smoking, the pathogenesis of atherosclerosis, and CHD have been robustly demonstrated and replicated, but that studies in Chinese populations are rare. The blood-based methylation of aryl-hydrocarbon receptor repressor (AHRR) cg05575921 and 6p21.33 cg06126421 has been associated with cardiovascular mortality in Caucasians. Here, we aim to investigate whether the AHRR and 6p21.33 methylation in the blood is associated with CHD in the Chinese population. Methods In this case–control study, 180 CHD patients recruited at their first registration in our study center, and 184 controls randomly selected from the people who participated in the annual health examination were enrolled. Methylation intensities of 19 CpG sites, including AHRR cg05575921, 6p21.33 cg06126421, and their flanking CpG sites, were quantified by mass spectrometry. The association between methylation intensities and CHD was estimated by logistic regression analyses adjusted for covariant. Results Compared to the controls, lower methylation of 6p21.33_CpG_4.5/cg06126421 was independently associated with increased odds of being a CHD patient (OR per − 10% methylation = 1.42 after adjustment for age, gender, and batch effect; p = 0.032 by multiple testing corrections). No association between blood-based AHRR methylation and CHD was found. Conclusions 6p21.33 methylation exhibits a significant association with CHD. The combination of 6p21.33 methylation and conventional risk factors might be an intermediate step towards the early detection of CHD.

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“…[8] F2RL3 gene has been shown to play a key role in mediating platelet activation, as well as a variety of signaling pathways, such as immune response, regulation of vascular endothelial cell activity, and inflammatory response. [9] Relevant studies have shown that epigenetic regulation of F2RL3 may increase platelet reactivity through protease activates receptor 4 function, thereby increasing the risk of morbidity and mortality of myocardial infarction. [10]…”

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Strong correlation between F2RL3 in the blood and osteoarthritis based on a retrospective cohort study

Shen

2023

Medicine

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Osteoarthritis (OA) is a common joint disease that mainly damages articular cartilage and involves the whole joint tissue. The purpose of this study was to explore the relationship between F2R Like Thrombin Or Trypsin Receptor 3 (F2RL3) and OA, so as to provide a new direction for the treatment of bone and joint. A total of 234 patients with OA were recruited. Clinical data was recorded and the expression levels of ELOVL Fatty Acid Elongase 7, F2RL3, glycoprotein IX platelet and Integrin Subunit Alpha 2b were measured. Pearson chi-square test and Spearman correlation coefficient were used to analyze the relationship between OA and related parameters. Univariate and multivariate Logistic regression were used for further analysis. Pearson chi-square test showed that F2RL3 (P < .001) was significantly associated with OA; Spearman correlation coefficient showed that OA and F2RL3 (ρ = −0.511, P < .001) significantly correlated; Univariate Logistic regression analysis showed that F2RL3 (odds ratio = 0.104, 95% confidence interval: 0.057-0.189, P < .001) was significantly associated with OA; multivariate logistic regression analysis showed that F2RL3 (odds ratio = 0.098, 95% confidence interval: 0.053-0.182, P < .001) were significantly associated with OA. The expression of F2RL3 is low in patients with OA. The lower the expression of F2RL3, the higher the probability of OA.

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F2RL3 Methylation in the Peripheral Blood as a Potential Marker for the Detection of Coronary Heart Disease: A Case-Control Study

Cited by 10 publications

References 55 publications

DNA methylation and cardiovascular disease in humans: a systematic review and database of known CpG methylation sites

DNA methylation and cardiovascular disease in humans: a systematic review and database of known CpG methylation sites

The association between DNA methylation of 6p21.33 and AHRR in blood and coronary heart disease in Chinese population

Strong correlation between F2RL3 in the blood and osteoarthritis based on a retrospective cohort study

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