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基于羊水代谢组学的唐氏综合征差异代谢物和代谢通路研究
作者:李雅红  张晓娟  张燕  杨佩颖  洪冬洋  孙云  王艳  胡平  许争峰  蒋涛 
单位:南京医科大学附属妇产医院/南京市妇幼保健院 遗传医学中心, 江苏 南京 210004
关键词:唐氏综合征 羊水 代谢组学 代谢通路 差异代谢物 
分类号:R34;R714.5
出版年·卷·期(页码):2021·49·第三期(263-269)
摘要:

目的:通过非靶向代谢组学的方法分析唐氏综合征(DS)胎儿母体羊水样本,探索DS差异代谢物及其相关代谢通路。方法:应用病例对照研究,6例DS胎儿母体羊水样本作为病例组,40例非DS胎儿母体羊水样本作为对照组,气相色谱飞行时间质谱(GC-TOF-MS)检测所有样本。采用正交偏最小二乘法判别分析(OPLS-DA)分析两组代谢轮廓的差异,通过多维和单维统计分析DS差异代谢物,并通过京都基因与基因组(KEGG)数据库对DS相关代谢通路进行分析。结果:OPLS-DA模型分析显示病例组与对照组间存在明显分离趋势,共发现23种同时满足单维和多维差异具有统计学意义的代谢物,包括1-甲基组氨酸、焦谷氨酸/谷氨酸值和α-酮异戊酸/缬氨酸值等。氨酰基-tRNA的生物合成、氮代谢、支链氨基酸代谢、谷氨酰胺和谷氨酸代谢等多条代谢通路被扰动。结论:羊水代谢组学研究显示DS存在多种代谢物变化,且多条代谢通路被扰动。

Objective: To explore differential metabolites and metabolic pathways associated with Down syndrome(DS) based on the analysis of fetal maternal amniotic fluid samples by untargeted metabolomics approach. Methods: In a case-control study, 6 DS fetal maternal amniotic fluid samples and 40 non DS fetal maternal amniotic fluid samples were considered as case and control groups, and all samples were analyzed using gas chromatography time-of-flight/mass spectrometry(GC-TOF-MS). Orthogonal partial least square discrimination analysis(OPLS-DA) model was built to observe the difference in metabolomics between the two groups. Multivariate and univariate analyses were used to explore DS differential metabolites, and the pathways involved were analyzed by Kyoto encyclopedia of genes and genomes(KEGG) database. Results: OPLS-DA model analysis showed a significant separation trend between case group and control group. A total of 23 metabolites, including 1-methylhistidine, pyroglutamic acid/glutamic acid ratio and α-ketoisovaleric acid/valine ratio were statistical differences meeting both univariate and multivariate statistical analysis. Metabolic pathway analysis revealed several metabolic pathways changed, including aminoacyl-tRNA biosynthesis; nitrogen metabolism; branched-chain amino acids metabolism; glutamine and glutamic acid metabolism; etc.Conclusion: Amniotic fluid metabolomics studies showed that multiple metabolites and metabolic pathways were disturbed in DS.

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