Department of Orthopedics, Affiliated Hospital of Qingdao University, Qingdao, China.
Shanxian Central Hospital, Heze, Shandong Province, China.
Pediatr Rheumatol Online J. 2024 May 9;22(1):51. doi: 10.1186/s12969-024-00986-0.
Juvenile Idiopathic Arthritis (JIA) is a condition that occurs when individuals under the age of 16 develop arthritis that lasts for more than six weeks, and the cause is unknown. The development of JIA may be linked to serum metabolites. Nevertheless, the association between JIA pathogenesis and serum metabolites is unclear, and there are discrepancies in the findings across studies.
In this research, the association between JIA in humans and 486 serum metabolites was assessed using genetic variation data and genome-wide association study. The identification of causal relationships was accomplished through the application of univariate Mendelian randomization (MR) analysis. Various statistical methods, including inverse variance weighted and MR-Egger, were applied to achieve this objective. To ensure that the findings from the MR analysis were trustworthy, a number of assessments were carried out. To ensure the accuracy of the obtained results, a range of techniques were utilised including the Cochran Q test, examination of the MR-Egger intercept, implementation of the leave-one-out strategy, and regression analysis of linkage disequilibrium scores. In order to identify the specific metabolic pathways associated with JIA, our primary objective was to perform pathway enrichment analysis using the Kyoto Encyclopedia of Genes and Genomes.
Two-sample summary data MR analyses and sensitivity analyses showed that five metabolites were significantly causally associated with JIA, including two risk factors-kynurenine (odds ratio [OR]: 16.39, 95% confidence interval [CI]: 2.07-129.63, p = 5.11 × 10) and linolenate (OR: 16.48, 95% CI: 1.32-206.22, p = 0.030)-and three protective factors-3-dehydrocarnitine (OR: 0.32, 95% CI: 0.14-0.72, p = 0.007), levulinate (4-oxovalerate) (OR: 0.40, 95% CI: 0.20-0.80, p = 0.010), and X-14,208 (phenylalanylserine) (OR: 0.68, 95% CI: 0.51-0.92, p = 0.010). Furthermore, seven metabolic pathways, including α-linolenic acid metabolism and pantothenate and CoA biosynthesis, are potentially associated with the onset and progression of JIA.
Five serum metabolites, including kynurenine and 3-dehydrocarnitine, may be causally associated with JIA. These results provide a theoretical framework for developing effective JIA prevention and screening strategies.
青少年特发性关节炎（JIA）是一种在 16 岁以下人群中发生的关节炎，持续时间超过六周，病因不明的疾病。JIA 的发生可能与血清代谢物有关。然而，JIA 发病机制与血清代谢物之间的关联尚不清楚，并且不同研究的结果存在差异。
本研究使用遗传变异数据和全基因组关联研究评估了人类 JIA 与 486 种血清代谢物之间的关联。通过应用单变量 Mendelian 随机化（MR）分析来确定因果关系。使用多种统计方法，包括逆方差加权和 MR-Egger 分析来实现这一目标。为了确保 MR 分析结果的可信度，进行了多项评估。为了确保获得结果的准确性，使用了多种技术，包括 Cochran Q 检验、MR-Egger 截距检验、单样本缺失策略和连锁不平衡得分回归分析。为了确定与 JIA 相关的特定代谢途径，我们的主要目标是使用京都基因与基因组百科全书（KEGG）进行途径富集分析。
两样本汇总数据 MR 分析和敏感性分析表明，有五种代谢物与 JIA 存在显著的因果关系，包括两种风险因素-犬尿氨酸（OR：16.39，95%置信区间 [CI]：2.07-129.63，p=5.11×10）和亚油酸（OR：16.48，95% CI：1.32-206.22，p=0.030）-和三种保护因素-3-脱氢肉碱（OR：0.32，95% CI：0.14-0.72，p=0.007）、戊二酸盐（4-氧代戊酸）（OR：0.40，95% CI：0.20-0.80，p=0.010）和 X-14,208（苯丙氨酰丝氨酸）（OR：0.68，95% CI：0.51-0.92，p=0.010）。此外，包括α-亚麻酸代谢和泛酸和 CoA 生物合成在内的七种代谢途径可能与 JIA 的发生和进展有关。
犬尿氨酸和 3-脱氢肉碱等五种血清代谢物可能与 JIA 存在因果关系。这些结果为制定有效的 JIA 预防和筛查策略提供了理论依据。
