Song Aifeng, Kang Lin, Cao Saixia, Wang Yafang, Li Huiyun
Department of Rheumatology and Immunology, Inner Mongolia Autonomous Region People's Hospital, Hohhot, China.
Department of Clinical Laboratory, Inner Mongolia Autonomous Region People's Hospital, Hohhot, China.
Medicine (Baltimore). 2025 Sep 5;104(36):e44304. doi: 10.1097/MD.0000000000044304.
Polymyalgia rheumatica (PMR) is a prevalent chronic inflammatory disorder among the elderly, presenting diagnostic and therapeutic challenges. Existing treatments like glucocorticoids have significant side effects, and the molecular mechanisms of PMR remain unclear. This study employed a 2-sample bidirectional Mendelian randomization approach to explore the causal relationship between 1091 metabolites, 309 metabolite ratios, and PMR risk. genome-wide association study data from large-scale cohorts were utilized, including metabolite data from 8299 Europeans and PMR datasets from FinnGen R12. After identifying suitable genetic instrumental variables and conducting multiple statistical analyses, 13 metabolites were found to be significantly associated with PMR risk at a P <.05 significance level. Among them, 10 metabolites increased the risk, 3 decreased it, and 1 had bidirectional effects. Five androgen-related metabolites were identified as causal risk factors, while one reduced the risk. Four arachidonic acid-related metabolites and 1 ratio increased the risk, and 1-stearoyl - 2-linoleoyl - gpc (18:0/18:2) also promoted PMR development. Cysteinylglycine was found to reduce the risk, but PMR increased its metabolite levels in serum. However, the study has limitations. The genome-wide association study data mainly came from European-ancestry populations, limiting generalizability, and the functional roles and mechanistic links of some metabolites remain unclear. Despite these limitations, this study provides new insights into PMR pathogenesis and potential metabolite-based intervention targets, highlighting the need for further research in diverse ethnic groups to better understand the relationship between metabolites and PMR.
风湿性多肌痛（PMR）是老年人中一种常见的慢性炎症性疾病，在诊断和治疗方面存在挑战。现有的治疗方法如糖皮质激素有显著的副作用，且PMR的分子机制仍不清楚。本研究采用两样本双向孟德尔随机化方法，探讨1091种代谢物、309种代谢物比率与PMR风险之间的因果关系。利用了来自大规模队列的全基因组关联研究数据，包括来自8299名欧洲人的代谢物数据和FinnGen R12的PMR数据集。在确定合适的基因工具变量并进行多项统计分析后，发现13种代谢物在P<0.05的显著性水平上与PMR风险显著相关。其中，10种代谢物增加风险，3种降低风险，1种具有双向作用。鉴定出5种雄激素相关代谢物为因果风险因素，而1种降低风险。4种花生四烯酸相关代谢物和1种比率增加风险，1-硬脂酰-2-亚油酰-gpc（18:0/18:2）也促进PMR发展。发现半胱氨酰甘氨酸降低风险，但PMR会增加其血清代谢物水平。然而，该研究存在局限性。全基因组关联研究数据主要来自欧洲血统人群，限制了普遍性，且一些代谢物的功能作用和机制联系仍不清楚。尽管有这些局限性，本研究为PMR发病机制和潜在的基于代谢物的干预靶点提供了新见解，强调需要在不同种族群体中进行进一步研究，以更好地理解代谢物与PMR之间的关系。
