A recent study led by Kasher and colleagues has identified glycoprotein Acetyls (GlycA) as a promising new biomarker for predicting cardiovascular complications in individuals with rheumatoid arthritis (RA). The research published in International Journal of Molecular Sciences utilized data from the UK Biobank, aimed to determine whether GlycA could explain the increased risk of cardiovascular disease (CVD) in RA patients, beyond that posed by traditional lipid risk factors.
The study examined associations among RA, atherosclerosis, GlycA, and major lipid factors such as total cholesterol, high-density lipoprotein (HDL), low-density lipoprotein (LDL), and triglycerides. By collecting genome-wide association study summary statistics from various resources, the researchers were able to perform detailed genetic analyses. Using Mendelian Randomization analysis to test causality among the variables, the researchers found that the genetic relationships between GlycA and RA, as well as between RA and atherosclerosis, were explained by horizontal pleiotropy (p-value = 0.001 and <0.001, respectively). However, GlycA appeared to predict atherosclerosis (p-value = 0.017) causally. Further investigation through colocalization analysis revealed several functionally relevant genes shared between GlycA and the assessed variables. Notably, two loci— the HLA region and SLC22A1—were consistently observed in all tested relationships.
GlycA is a biomarker identified through nuclear magnetic resonance spectroscopy analysis of blood plasma. It mirrors the glycosylation status of several acute-phase proteins such as alpha-1-acid glycoprotein, haptoglobin, alpha-1-antichymotrypsin, and alpha-1-antitrypsin. Proposed for assessing inflammation in RA and other autoimmune disorders, GlycA also serves in evaluating CVD risk. It reflects the clinical profile of RA patients, indicating both inflammatory status and CVD risk, capturing acute and chronic inflammation and correlating with disease severity in inflammatory contexts. The findings of study by Kasher et al. revealed that elevated levels of GlycA in RA patients correlated with increased cardiovascular risk and predicted poorer treatment response. GlycA’s integration into risk assessment models improved detection of atherosclerosis and identified patients with impaired lipid metabolism. These findings highlight GlycA’s potential as a valuable tool for early CV risk stratification and personalized treatment management in RA.
The findings suggest that GlycA plays a mediating role in the RA-atherosclerosis relationship through various pathways. While GlycA is pleiotropically related to RA, it also appears to causally predict atherosclerosis, highlighting its significance in the development of atherosclerosis in RA patients. This study marks a significant step forward in understanding the complex interplay between RA and cardiovascular disease, positioning GlycA as a crucial biomarker in predicting and potentially managing cardiovascular complications in RA patients.
Reference
- Kasher M, Freidin MB, Williams FMK, Cherny SS, Ashkenazi S, Livshits G. Glycoprotein Acetyls Is a Novel Biomarker Predicting Cardiovascular Complications in Rheumatoid Arthritis. Int J Mol Sci. 2024 May 30;25(11):5981.
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- Ballout RA, Remaley AT. GlycA: A New Biomarker for Systemic Inflammation and Cardiovascular Disease (CVD) Risk Assessment. J Lab Precis Med. 2020 Apr;5:17.