Department of Dermatology, Shenzhen Second People's Hospital, The First Affiliated Hospital of Shenzhen University, Shenzhen, 518035, Guangdong, China.
Arch Dermatol Res. 2024 Aug 23;316(8):565. doi: 10.1007/s00403-024-03294-5.
Two-sample Mendelian randomization (TSMR) was employed to examine the association between lipidome and five inflammatory skin diseases.
To evaluate the association between various molecular subtypes of lipidome and the risk of five inflammatory skin diseases, we analyzed a comprehensive GWAS dataset comprising 179 lipidome. The Two-Sample Mendelian Randomization (TSMR) method was employed to investigate causal relationships. Heterogeneity and pleiotropy were assessed using Cochran's Q test, MR-Egger intercept test, and MR-PRESSO global test. Additionally, a sensitivity analysis was conducted to evaluate the influence of individual single nucleotide polymorphisms on Mendelian Randomization study.
Using 179 serum lipidome as exposures and five common inflammatory skin diseases as outcomes, we investigated their associations in this large-scale study. Our findings reveal significant impacts of glycerophospholipids, glycerolipids, and sphingomyelins on inflammatory skin diseases. Glycerophospholipids were protective against pemphigus but predominantly posed risks for other inflammatory skin diseases. Specifically, phosphatidylcholine (16:0_0:0) exhibited the most significant risk association with lichen planus (OR = 1.25, 95% CI 1.11-1.40, P < 0.001). Conversely, glycerolipids showed no effect on lichen planus but were protective against pemphigus while potentially posing risks for other conditions. Triacylglycerol (46:2) showed the most substantial risk association with vitiligo (OR = 1.99, 95% CI 1.35-2.93, P < 0.001). Furthermore, sphingomyelins had no effect on atopic dermatitis but posed potential risks for other inflammatory skin diseases. Sphingomyelin (d40:1) notably emerged as a significant risk factor for pemphigus (OR = 1.91, 95% CI 1.37-2.66, P < 0.001).
This study has elucidated the potential harmful effects of glycerophospholipids, glycerolipids, and sphingomyelins on inflammatory skin diseases, while also providing valuable insights for future research into the pathophysiology, prevention and treatment of these conditions.
采用两样本 Mendelian 随机化（TSMR）研究脂质组与五种炎症性皮肤病之间的关联。
为了评估各种脂质组分子亚型与五种炎症性皮肤病风险之间的关联，我们分析了一个包含 179 个脂质组的综合 GWAS 数据集。采用两样本 Mendelian 随机化（TSMR）方法来研究因果关系。使用 Cochran's Q 检验、MR-Egger 截距检验和 MR-PRESSO 全局检验评估异质性和多效性。此外，还进行了敏感性分析，以评估单个单核苷酸多态性对 Mendelian Randomization 研究的影响。
使用 179 种血清脂质组作为暴露因素，将五种常见炎症性皮肤病作为结局，在这项大规模研究中我们对它们的相关性进行了研究。研究结果表明，甘油磷脂、甘油三酯和神经鞘脂与炎症性皮肤病有显著关联。甘油磷脂对天疱疮具有保护作用，但主要对其他炎症性皮肤病有风险。具体而言，磷脂酰胆碱（16:0_0:0）与扁平苔藓的关联最为显著（OR=1.25，95%CI 1.11-1.40，P<0.001）。相反，甘油三酯对扁平苔藓没有影响，但对天疱疮有保护作用，同时对其他疾病有潜在风险。三酰甘油（46:2）与白癜风的关联最为显著（OR=1.99，95%CI 1.35-2.93，P<0.001）。此外，神经鞘脂对特应性皮炎没有影响，但对其他炎症性皮肤病有潜在风险。神经鞘磷脂（d40:1）显著成为天疱疮的危险因素（OR=1.91，95%CI 1.37-2.66，P<0.001）。
本研究阐明了甘油磷脂、甘油三酯和神经鞘脂对炎症性皮肤病的潜在有害影响，为这些疾病的病理生理学、预防和治疗的进一步研究提供了有价值的见解。
