Department of Hematology, the First Affiliated Hospital of Wannan Medical College, Wuhu, China.
Department of Hematology, the First Affiliated Hospital of Wannan Medical College, Wuhu, China
Ann Clin Lab Sci. 2024 Jul;54(4):430-445.
Immune thrombocytopenia (ITP) is a common bleeding disorder. Although global lipidomic analyses have identified a potential role for lipid species in platelet function, there is currently no evidence to support a causal relationship between plasma lipids and ITP. To investigate this further, we conducted a two-sample Mendelian randomization analysis to determine whether there is a genetically predicted causal relationship between 179 plasma lipid groups and ITP.
Genome-wide association data from 179 plasma lipid species from 7,174 Finnish subjects were used in a preliminary analysis of ITP GWAS data from the GWAS catalogue database (GCST90018865, case=675, control=488,749). Causal analyses were performed using random inverse variance weighting (IVW) with MR-Egger and weighted median as complementary analyses. Sensitivity analyses were conducted using the MR-Egger intercept test, MR-PRESSO, and leave-one-out analysis. To assess the association of lipid metabolites with the risk of developing ITP, multivariate MR analysis was performed. Significant correlations were found. The final identification of lipid metabolites was further evaluated using the Steiger test for chain imbalance.
The results of this study showed that six plasma lipid species, sterol esters (27:1/20:2) (SE) (odds ratio [OR]: 1.30, 95% confidence interval [CI]: 1.06-1.60, =0.013), phosphatidylethanolamine (18:0_0:0) (PE) (OR: 1. 46, 95% CI: 1.10-1.95, =0.009), phosphatidylcholine (16:0_18:3) (PC) (OR: 1.51, 95% CI: 1.12-2.02, =0.006), phosphatidylcholine-ether (O-16:0_16:0) (PCO) (OR: 0.64, 95% CI: 0. 47-0.88, p = 0.005), phosphatidylethanolamine-ether (O-18:2_20:4) (PEO) (OR: 0.71, 95% CI: 0.55-0.93, =0.013), triacylglycerol (49:1) (TAG) (OR: 1.65, 95% CI: 1.21-2.24, =0.001), and ITP were all significantly correlated. MVMR analysis showed that genetically predicted phosphatidylcholine ethers may independently influence ITP without dependence on other metabolites. Triacylglycerol may be affected by other plasma liposomal metabolites and is a risk factor for the development of ITP.
The current work provides evidence for a causal role of six plasma lipids in ITP and provides new perspectives for combining genomics and metabolomics to explore the biological mechanisms of ITP. These findings may contribute to the screening, prevention, and treatment of ITP.
免疫性血小板减少症(ITP)是一种常见的出血性疾病。尽管全球脂质组学分析已经确定了脂质种类在血小板功能中的潜在作用,但目前没有证据支持血浆脂质与 ITP 之间存在因果关系。为了进一步研究这一问题,我们进行了两样本孟德尔随机化分析,以确定 179 种血浆脂质与 ITP 之间是否存在遗传预测的因果关系。
使用来自 7174 名芬兰受试者的 179 种血浆脂质的全基因组关联数据,对 GWAS 目录数据库(GCST90018865,病例=675,对照=488749)中的 ITP GWAS 数据进行初步分析。使用随机逆方差加权(IVW)进行因果分析,并使用加权中位数作为补充分析。使用 MR-Egger 截距检验、MR-PRESSO 和单样本剔除分析进行敏感性分析。为了评估脂质代谢物与 ITP 发病风险的关联,进行了多变量 MR 分析。发现了显著的相关性。使用链不平衡的 Steiger 检验进一步评估了脂质代谢物的最终鉴定。
本研究结果表明,六种血浆脂质,甾醇酯(27:1/20:2)(SE)(比值比[OR]:1.30,95%置信区间[CI]:1.06-1.60,=0.013),磷脂酰乙醇胺(18:0_0:0)(PE)(OR:1.46,95% CI:1.10-1.95,=0.009),磷脂酰胆碱(16:0_18:3)(PC)(OR:1.51,95% CI:1.12-2.02,=0.006),磷脂酰胆碱醚(O-16:0_16:0)(PCO)(OR:0.64,95% CI:0.47-0.88,p=0.005),磷脂酰乙醇胺醚(O-18:2_20:4)(PEO)(OR:0.71,95% CI:0.55-0.93,=0.013),三酰基甘油(49:1)(TAG)(OR:1.65,95% CI:1.21-2.24,=0.001),与 ITP 均呈显著相关。MVMR 分析表明,遗传预测的磷脂酰胆碱醚可能独立影响 ITP,而不依赖于其他代谢物。三酰基甘油可能受其他血浆脂蛋白代谢物的影响,是 ITP 发病的危险因素。
目前的工作为六种血浆脂质在 ITP 中的因果作用提供了证据,并为结合基因组学和代谢组学探索 ITP 的生物学机制提供了新的视角。这些发现可能有助于 ITP 的筛查、预防和治疗。