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Article: Glycoprotein Acetyls Is a Novel Biomarker Predicting Cardiovascular Complications in Rheumatoid Arthritis
Title | Glycoprotein Acetyls Is a Novel Biomarker Predicting Cardiovascular Complications in Rheumatoid Arthritis |
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Authors | |
Keywords | atherosclerosis GlycA inflammation lipid factors pleiotropy rheumatoid arthritis |
Issue Date | 1-Jun-2024 |
Publisher | Multidisciplinary Digital Publishing Institute (MDPI) |
Citation | International Journal of Molecular Sciences, 2024, v. 25, n. 11 How to Cite? |
Abstract | The relationship between rheumatoid arthritis (RA) and early onset atherosclerosis is well depicted, each with an important inflammatory component. Glycoprotein acetyls (GlycA), a novel biomarker of inflammation, may play a role in the manifestation of these two inflammatory conditions. The present study examined a potential mediating role of GlycA within the RA–atherosclerosis relationship to determine whether it accounts for the excess risk of cardiovascular disease over that posed by lipid risk factors. The UK Biobank dataset was acquired to establish associations among RA, atherosclerosis, GlycA, and major lipid factors: total cholesterol (TC), high- and low-density lipoprotein (HDL, LDL) cholesterol, and triglycerides (TGs). Genome-wide association study summary statistics were collected from various resources to perform genetic analyses. Causality among variables was tested using Mendelian Randomization (MR) analysis. Genes of interest were identified using colocalization analysis and gene enrichment analysis. MR results appeared to indicate that the genetic relationship between GlycA and RA and also between RA and atherosclerosis was explained by horizontal pleiotropy (p-value = 0.001 and <0.001, respectively), while GlycA may causally predict atherosclerosis (p-value = 0.017). Colocalization analysis revealed several functionally relevant genes shared between GlycA and all the variables assessed. Two loci were apparent in all relationships tested and included the HLA region as well as SLC22A1. GlycA appears to mediate the RA–atherosclerosis relationship through several possible pathways. GlycA, although pleiotropically related to RA, appears to causally predict atherosclerosis. Thus, GlycA is suggested as a significant factor in the etiology of atherosclerosis development in RA. |
Persistent Identifier | http://hdl.handle.net/10722/345746 |
ISSN | 2023 Impact Factor: 4.9 2023 SCImago Journal Rankings: 1.179 |
DC Field | Value | Language |
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dc.contributor.author | Kasher, Melody | - |
dc.contributor.author | Freidin, Maxim B | - |
dc.contributor.author | Williams, Frances MK | - |
dc.contributor.author | Cherny, Stacey S | - |
dc.contributor.author | Ashkenazi, Shai | - |
dc.contributor.author | Livshits, Gregory | - |
dc.date.accessioned | 2024-08-27T09:10:54Z | - |
dc.date.available | 2024-08-27T09:10:54Z | - |
dc.date.issued | 2024-06-01 | - |
dc.identifier.citation | International Journal of Molecular Sciences, 2024, v. 25, n. 11 | - |
dc.identifier.issn | 1661-6596 | - |
dc.identifier.uri | http://hdl.handle.net/10722/345746 | - |
dc.description.abstract | <p>The relationship between rheumatoid arthritis (RA) and early onset atherosclerosis is well depicted, each with an important inflammatory component. Glycoprotein acetyls (GlycA), a novel biomarker of inflammation, may play a role in the manifestation of these two inflammatory conditions. The present study examined a potential mediating role of GlycA within the RA–atherosclerosis relationship to determine whether it accounts for the excess risk of cardiovascular disease over that posed by lipid risk factors. The UK Biobank dataset was acquired to establish associations among RA, atherosclerosis, GlycA, and major lipid factors: total cholesterol (TC), high- and low-density lipoprotein (HDL, LDL) cholesterol, and triglycerides (TGs). Genome-wide association study summary statistics were collected from various resources to perform genetic analyses. Causality among variables was tested using Mendelian Randomization (MR) analysis. Genes of interest were identified using colocalization analysis and gene enrichment analysis. MR results appeared to indicate that the genetic relationship between GlycA and RA and also between RA and atherosclerosis was explained by horizontal pleiotropy (p-value = 0.001 and <0.001, respectively), while GlycA may causally predict atherosclerosis (p-value = 0.017). Colocalization analysis revealed several functionally relevant genes shared between GlycA and all the variables assessed. Two loci were apparent in all relationships tested and included the HLA region as well as SLC22A1. GlycA appears to mediate the RA–atherosclerosis relationship through several possible pathways. GlycA, although pleiotropically related to RA, appears to causally predict atherosclerosis. Thus, GlycA is suggested as a significant factor in the etiology of atherosclerosis development in RA.</p> | - |
dc.language | eng | - |
dc.publisher | Multidisciplinary Digital Publishing Institute (MDPI) | - |
dc.relation.ispartof | International Journal of Molecular Sciences | - |
dc.rights | This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License. | - |
dc.subject | atherosclerosis | - |
dc.subject | GlycA | - |
dc.subject | inflammation | - |
dc.subject | lipid factors | - |
dc.subject | pleiotropy | - |
dc.subject | rheumatoid arthritis | - |
dc.title | Glycoprotein Acetyls Is a Novel Biomarker Predicting Cardiovascular Complications in Rheumatoid Arthritis | - |
dc.type | Article | - |
dc.description.nature | published_or_final_version | - |
dc.identifier.doi | 10.3390/ijms25115981 | - |
dc.identifier.pmid | 38892172 | - |
dc.identifier.scopus | eid_2-s2.0-85195823116 | - |
dc.identifier.volume | 25 | - |
dc.identifier.issue | 11 | - |
dc.identifier.eissn | 1422-0067 | - |
dc.identifier.issnl | 1422-0067 | - |