NMR-based Metabonomics Study On Plasma And Urine Of Nonsyndromic Cleft Lip And/or Palates

Objective:To study the metabolic changes of plasma and urine of nonsyndromic cleft lip and/or palates (NSCL/P) patients and normal human using nuclear magnetic resonance (NMR) based metabonomics approach, so as to establish the'H NMR fingerprint of plasma and urine of NSCL/P, analyze the characteristics of abnormal metabolites with NSCL/P, and evaluate the feasibility of employing metabonomics technology in clinical application.Methods:The experiments were divided into NSCL/P group and control group. The plasma samples were obtained from 27 patients coming from NSCL/P and 26 healthy controls, and the urine samples were acquired from 17 patients coming from NSCL/P and 13 healthy controls. NMR spectroscopy was used for acquired plasma and urine metabolic profiles of NSCL/P, so as to determinate one-dimensional 1H NMR spectroscopy of plasma and urine from CL/P; principal component analysis (PCA) was utilized to analyze the NMR data, so as to study the metabolic difference of plasma and urine with NSCL/P group and normal control group, and access to the specific metabolic markers of NSCL/P.Results:The 1H NMR spectroscopy analysis indicated that, comparing with the 1H NMR spectra of healthy controls and the NSCL/P patients, those of patients with NSCL/P showed a certain difference of plasma in the range ofδ0.8～1.5,δ2.0～2.2 andδ3.0～4.0 (e.g.δ0.97,δ1.04,δ1.33,δ1.48,δ2.02～2.06,δ3.05,δ4.06,δ3.89,δ4.14), and some difference of urine in the range ofδ1.0～1.5,δ2.0～3.0,δ3.5～4.5 andδ6.6～8.5 (e.g.δ1.04,δ1.34,δ4.14,δ2.06～2.08,δ2.19,δ2.24,δ2.42,δ2.56,δ2.72,δ2.84,δ2.92,δ3.74,δ4.25,δ6.89,δ7.15,δ7.25,δ7.74,δ8.44,δ7.64,δ7.76), that was, the possible peak of NSCL/P. PCA analysis showed significant difference between NMR-based metabolic profiles of plasma and urine samples from the NSCL/P group and control group. Comparing with the control group, the plasma concentration of valine, lactate, alanine, glycoprotein, creatinine, creatine and other substances were significantly decreased in the NSCL/P group; the urine concentration of valine, lactate, glycoprotein, fatty acid, succinic acid, citrate, aspartic acid,β-glucose, tyrosine, formate and other metabolites were decreased, and hippurate, threonine, chloroform, dimethyl-formamide, phenylalanine, benzene, and other metabolites were significantly increased in the NSCL/P group.Conclusion:It is helpful to establish the NMR fingerprint of NSCL/P by 1H NMR spectra of plasma and urine from patients; NMR-based metabonomics approach can clearly reveal the metabolic changes of plasma and urine in NSCL/P patients, and acquire the characteristics of abnormal metabolites with NSCL/P; Metabonomics will likely be a studying method for the mechanism of congenital diseases.