School of Acupuncture and Tuina, Chengdu University of Traditional Chinese Medicine, Chengdu, China.
School of Health and Rehabilitation, Chengdu University of Traditional Chinese Medicine, Chengdu, China.
PLoS One. 2024 Feb 28;19(2):e0298629. doi: 10.1371/journal.pone.0298629. eCollection 2024.
Past studies have demonstrated that patients diagnosed with rheumatoid arthritis (RA) often exhibit abnormal levels of lipids. Furthermore, certain lipid-modifying medications have shown effectiveness in alleviating clinical symptoms associated with RA. However, the current understanding of the causal relationship between lipids, lipid-modifying medications, and the risk of developing RA remains inconclusive. This study employed Mendelian randomization (MR) to investigate the causal connection between lipids, lipid-modifying drugs, and the occurrence of RA.
We obtained genetic variation for lipid traits and drug targets related to lipid modification from three sources: the Global Lipids Genetics Consortium (GLGC), UK Biobank, and Nightingale Health 2020. The genetic data for RA were acquired from two comprehensive meta-analyses and the R8 of FINNGEN, respectively. These variants were employed in drug-target MR analyses to establish a causal relationship between genetically predicted lipid-modifying drug targets and the risk of RA. For suggestive lipid-modified drug targets, we conducted Summary-data-based Mendelian Randomization (SMR) analyses and using expression quantitative trait loci (eQTL) data in relevant tissues. In addition, we performed co-localization analyses to assess genetic confounders.
Our analysis revealed no significant causal relationship between lipid and RA. We observed that the genetically predicted 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) -mediated low density lipoprotein cholesterol (LDL-C) (OR 0.704; 95% CI 0.56, 0.89; P = 3.43×10-3), Apolipoprotein C-III (APOC3) -mediated triglyceride (TG) (OR 0.844; 95% CI 0.77, 0.92; P = 1.50×10-4) and low density lipoprotein receptor (LDLR) -mediated LDL-C (OR 0.835; 95% CI 0.73, 0.95; P = 8.81×10-3) were significantly associated with a lowered risk of RA. while Apolipoprotein B-100 (APOB) -mediated LDL-C (OR 1.212; 95%CI 1.05,1.40; P = 9.66×10-3) was significantly associated with an increased risk of RA.
Our study did not find any supporting evidence to suggest that lipids are a risk factor for RA. However, we observed significant associations between HMGCR, APOC3, LDLR, and APOB with the risk of RA.
既往研究表明，类风湿关节炎（RA）患者常表现出脂质水平异常。此外，某些调脂药物在缓解 RA 相关临床症状方面具有疗效。然而，目前对于脂质、调脂药物与 RA 发病风险之间的因果关系仍存在争议。本研究采用孟德尔随机化（MR）方法，探讨脂质、调脂药物与 RA 发病之间的因果关系。
我们从三个来源获得了脂质特征和与脂质修饰相关的药物靶点的遗传变异：全球脂质遗传学联盟（GLGC）、英国生物库（UK Biobank）和 2020 年奈廷格尔健康研究（Nightingale Health 2020）。RA 的遗传数据分别来自两项综合荟萃分析和 FINNGEN 的 R8。这些变异用于药物靶点 MR 分析，以确定遗传预测的调脂药物靶点与 RA 发病风险之间的因果关系。对于提示性的调脂药物靶点，我们进行了基于汇总数据的孟德尔随机化（SMR）分析，并使用相关组织中的表达数量性状基因座（eQTL）数据。此外，我们进行了共定位分析以评估遗传混杂因素。
本研究未发现脂质与 RA 之间存在因果关系。我们观察到，遗传预测的羟甲基戊二酰辅酶 A 还原酶（HMGCR）介导的低密度脂蛋白胆固醇（LDL-C）（OR 0.704；95%CI 0.56，0.89；P = 3.43×10-3）、载脂蛋白 C-III（APOC3）介导的甘油三酯（TG）（OR 0.844；95%CI 0.77，0.92；P = 1.50×10-4）和低密度脂蛋白受体（LDLR）介导的 LDL-C（OR 0.835；95%CI 0.73，0.95；P = 8.81×10-3）与 RA 发病风险降低显著相关，而载脂蛋白 B-100（APOB）介导的 LDL-C（OR 1.212；95%CI 1.05，1.40；P = 9.66×10-3）与 RA 发病风险升高显著相关。
本研究未发现脂质是 RA 发病风险因素的证据，但观察到 HMGCR、APOC3、LDLR 和 APOB 与 RA 发病风险之间存在显著关联。
