Xiaohang Chen1, Hongyan Chen2, Haimei Nie3, Gaochi Li1, Jinjiang Su4, Xianzhen Cao1, Yongli Cao5, Fengxiang Wei6,7,8. 1. The Genetics Laboratory, Longgang District Maternity & Child Healthcare Hospital of Shenzhen City, Shenzhen, 518000, China. 2. Department of Nursing, Guangdong Pharmaceutical University, Guangzhou, 510000, China. 3. Department of Gynecology, Longgang District Maternity & Child Healthcare Hospital of Shenzhen City, Shenzhen, 518000, China. 4. Department of Cell Biology, Jiamusi University, Jiamusi, 154000, China. 5. Department of Obstetrics, Longgang District Maternity & Child Healthcare Hospital of Shenzhen City, Shenzhen, 518000, China. 6. The Genetics Laboratory, Longgang District Maternity & Child Healthcare Hospital of Shenzhen City, Shenzhen, 518000, China. haowei727499@163.com. 7. Department of Nursing, Guangdong Pharmaceutical University, Guangzhou, 510000, China. haowei727499@163.com. 8. Department of Cell Biology, Jiamusi University, Jiamusi, 154000, China. haowei727499@163.com.
Abstract
INTRODUCTION: α-Thalassemia is the most common inherited disease in southern China. The severest form is hemoglobin (Hb) Bart's disease, in which the affected fetuses almost always die in utero or shortly after birth, and the mothers are at high risk for severe morbidity. OBJECTIVE: To investigate the changes in all metabolites in fetuses with Hb Bart's disease and to characterize the metabolomic and lipidomic biomarkers in the development of Hb Bart's fetuses. METHODS: Amniotic fluid (AF) specimens were selected from 34 pregnant women who underwent interventional prenatal diagnosis from June 2017 to June 2018. Gap-PCR analysis was used to diagnose Hb Bart's disease, and untargeted metabolomic and lipidomic analyses were performed. RESULTS: By analyzing AF samples, 935 differential metabolites were selected between Hb Bart's and control fetuses. The metabolites with significant changes mainly involved D-glutamine and D-glutamate metabolism, histidine metabolism, arginine metabolism, beta-alanine metabolism and alanine, aspartate and glutamate metabolism. Further lipidomics analysis revealed 132 differential lipids, mainly involved phosphatidylcholine and triglyceride metabolism. Through the characterized metabolites in AF, a schematic model of Hb Bart's disease was established. CONCLUSION: Glutamate and glutathione metabolism, aspartate metabolism, urea metabolism and triglyceride metabolism were significantly changed in the Hb Bart's group compared to the control group. The characterized biomarkers were mainly involved in oxidative stress reaction, iron overload and liver dysfunction. This finding may help improve the treatment options for α-thalassemia as well as diagnosing phenotype of patients.
INTRODUCTION: α-Thalassemia is the most common inherited disease in southern China. The severest form is hemoglobin (Hb) Bart's disease, in which the affected fetuses almost always die in utero or shortly after birth, and the mothers are at high risk for severe morbidity. OBJECTIVE: To investigate the changes in all metabolites in fetuses with Hb Bart's disease and to characterize the metabolomic and lipidomic biomarkers in the development of Hb Bart's fetuses. METHODS: Amniotic fluid (AF) specimens were selected from 34 pregnant women who underwent interventional prenatal diagnosis from June 2017 to June 2018. Gap-PCR analysis was used to diagnose Hb Bart's disease, and untargeted metabolomic and lipidomic analyses were performed. RESULTS: By analyzing AF samples, 935 differential metabolites were selected between Hb Bart's and control fetuses. The metabolites with significant changes mainly involved D-glutamine and D-glutamate metabolism, histidine metabolism, arginine metabolism, beta-alanine metabolism and alanine, aspartate and glutamate metabolism. Further lipidomics analysis revealed 132 differential lipids, mainly involved phosphatidylcholine and triglyceride metabolism. Through the characterized metabolites in AF, a schematic model of Hb Bart's disease was established. CONCLUSION: Glutamate and glutathione metabolism, aspartate metabolism, urea metabolism and triglyceride metabolism were significantly changed in the Hb Bart's group compared to the control group. The characterized biomarkers were mainly involved in oxidative stress reaction, iron overload and liver dysfunction. This finding may help improve the treatment options for α-thalassemia as well as diagnosing phenotype of patients.
Authors: Manuel Liebeke; Michael W Bruford; Robert K Donnelly; Timothy M D Ebbels; Jie Hao; Peter Kille; Elma Lahive; Rachael M Madison; A John Morgan; Gabriela A Pinto-Juma; David J Spurgeon; Claus Svendsen; Jacob G Bundy Journal: Biol Lett Date: 2014-09 Impact factor: 3.703