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[摘要]
目的：使用孟德尔随机化研究的方法探究神经酰胺对视网膜静脉阻塞(RVO)的作用以及其中介调控关系。
方法：选取4种神经酰胺全基因组关联研究(GWAS)数据为暴露，选取芬兰数据库中RVO的GWAS数据为结局，研究其因果关系。此外，选取1 400种代谢产物的GWAS数据为待选择的中介因子，研究暴露到结局的中介作用。
结果：神经酰胺(d40：1)\〖IVW OR(95%CI)：0.750(0.604-0.930)，P<0.05\〗和神经酰胺(d42：2)\〖IVW OR(95%CI)：0.771(0.632-0.941)，P<0.05\〗与RVO有因果关联。神经酰胺(d40：1)通过介导3-甲基黄嘌呤、支链或直链或环丙基10：1脂肪酸、谷氨酰胺、羟基棕榈酰基鞘磷脂调控RVO的发生。神经酰胺(d42：2)通过介导N-甲基羟脯氨酸、支链或直链或环丙基 10：1 脂肪酸、N1-甲基腺苷、亮氨酸与N-棕榈酰肌氨酸的比率调控RVO的发生。
结论：神经酰胺(d40：1)和神经酰胺(d42：2)对RVO具有保护作用，其通过调控多种中介因子作用于RVO。
[Key word]
[Abstract]
AIM: To investigate the causal effects of ceramides on retinal vein occlusion(RVO)and elucidate their potential mediating mechanisms using Mendelian randomization(MR)analysis.
METHODS: Genome-wide association study(GWAS)data for four ceramide species were utilized as exposures, and RVO GWAS data from the FinnGen database as the outcome. Additionally, GWAS data for 1 400 intermediate metabolites were analyzed to identify potential mediators in the ceramide-RVO pathway.
RESULTS: Two ceramide species exhibited significant causal associations with RVO: ceramide(d40:1)\〖IVW OR(95% CI): 0.750(0.604-0.930), P<0.05\〗 and ceramide(d42:2)\〖IVW OR(95% CI): 0.771(0.632-0.941), P<0.05\〗, suggesting protective effects. Mediation analysis revealed that ceramide(d40:1)influenced RVO risk through metabolites including 3-methylxanthine, branched/straight-chain/cyclopropyl 10:1 fatty acids, glutamine, and hydroxypalmitoyl sphingomyelin. Similarly, ceramide(d42:2)acted via N-methylhydroxyproline, the same fatty acid group, N1-methyladenosine, and the leucine-to-N-palmitoyl-sarcosinate ratio.
CONCLUSION: Ceramides(d40:1)and(d42:2)confer protection against RVO, partially mediated by specific metabolic pathways.
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[基金项目]
