Department of Morphological Sciences, Adelson School of Medicine, Ariel University, Ariel 4070000, Israel.
Department of Biology, School of Biological and Behavioural Sciences, Queen Mary University of London, London E1 4NS, UK.
Int J Mol Sci. 2024 May 30;25(11):5981. doi: 10.3390/ijms25115981.
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 (-value = 0.001 and <0.001, respectively), while GlycA may causally predict atherosclerosis (-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 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.
类风湿关节炎（RA）与早发动脉粥样硬化之间的关系已经得到了很好的描述，两者都有重要的炎症成分。糖蛋白乙酰基（GlycA）是一种新的炎症生物标志物，可能在这两种炎症状态的表现中发挥作用。本研究探讨了 GlycA 在 RA-动脉粥样硬化关系中的潜在中介作用，以确定它是否解释了心血管疾病风险超过脂质风险因素的风险。本研究从英国生物库（UK Biobank）数据集中获取了 RA、动脉粥样硬化、GlycA 与主要脂质因素（总胆固醇（TC）、高密度脂蛋白（HDL）、低密度脂蛋白（LDL）胆固醇和甘油三酯（TGs））之间的关联。从各种资源中收集了全基因组关联研究汇总统计数据，以进行遗传分析。使用孟德尔随机化（MR）分析测试变量之间的因果关系。使用共定位分析和基因富集分析鉴定感兴趣的基因。MR 结果似乎表明，GlycA 与 RA 之间以及 RA 与动脉粥样硬化之间的遗传关系是由水平多效性解释的（-值分别为 0.001 和 <0.001），而 GlycA 可能会导致动脉粥样硬化（-值 = 0.017）。共定位分析揭示了 GlycA 与所有评估变量之间存在几个功能相关的基因。在所有测试的关系中都出现了两个位点，包括 HLA 区域以及 GlycA 似乎通过几种可能的途径介导 RA-动脉粥样硬化的关系。尽管 GlycA 与 RA 具有多效性相关，但它似乎会导致动脉粥样硬化。因此，GlycA 被认为是 RA 患者动脉粥样硬化发展病因学中的一个重要因素。
