Harville E W, Li Y-Y, Pan K, McRitchie S, Pathmasiri W, Sumner S
Department of Epidemiology, Tulane University School of Public Health and Tropical Medicine, Epidemiology #8318, 1440 Canal St. Ste. 2001, New Orleans, LA, 70112, USA.
Department of Nutrition, Nutrition Research Institute, University of North Carolina at Chapel Hill School of Public Health, CB#74612, Chapel Hill, NC, 27599-7461, USA.
Sci Rep. 2021 Feb 10;11(1):3468. doi: 10.1038/s41598-021-82804-1.
Understanding of causal biology and predictive biomarkers are lacking for hypertensive disorders of pregnancy (HDP) and preterm birth (PTB). First-trimester serum specimens from 51 cases of HDP, including 18 cases of pre-eclampsia (PE) and 33 cases of gestational hypertension (GH); 53 cases of PTB; and 109 controls were obtained from the Global Alliance to Prevent Prematurity and Stillbirth repository. Metabotyping was conducted using liquid chromatography high resolution mass spectroscopy and nuclear magnetic resonance spectroscopy. Multivariable logistic regression was used to identify signals that differed between groups after controlling for confounders. Signals important to predicting HDP and PTB were matched to an in-house physical standards library and public databases. Pathway analysis was conducted using GeneGo MetaCore. Over 400 signals for endogenous and exogenous metabolites that differentiated cases and controls were identified or annotated, and models that included these signals produced substantial improvements in predictive power beyond models that only included known risk factors. Perturbations of the aminoacyl-tRNA biosynthesis, L-threonine, and renal secretion of organic electrolytes pathways were associated with both HDP and PTB, while pathways related to cholesterol transport and metabolism were associated with HDP. This untargeted metabolomics analysis identified signals and common pathways associated with pregnancy complications.
目前对于妊娠高血压疾病（HDP）和早产（PTB）的因果生物学及预测生物标志物仍缺乏了解。从全球预防早产和死产联盟资料库中获取了51例HDP患者（包括18例先兆子痫（PE）和33例妊娠期高血压（GH））、53例PTB患者以及109名对照者的孕早期血清样本。采用液相色谱高分辨率质谱和核磁共振波谱进行代谢分型。使用多变量逻辑回归来识别在控制混杂因素后组间存在差异的信号。将对预测HDP和PTB重要的信号与内部物理标准库和公共数据库进行匹配。使用GeneGo MetaCore进行通路分析。识别或注释了400多个区分病例和对照的内源性和外源性代谢物信号，包含这些信号的模型在预测能力上比仅包含已知风险因素的模型有显著提高。氨酰-tRNA生物合成、L-苏氨酸以及有机电解质肾分泌途径的扰动与HDP和PTB均相关，而与胆固醇转运和代谢相关的途径与HDP相关。这项非靶向代谢组学分析确定了与妊娠并发症相关的信号和共同途径。
