title: β-Thalassemia Patients Revealed a Significant Change of Untargeted Metabolites in Comparison to Healthy Individuals.
abstract: β-Thalassemia is one of the most prevalent forms of congenital blood disorders characterized by reduced hemoglobin levels with severe complications, affecting all dimensions of life. The mechanisms underlying the phenotypic heterogeneity of β-thalassemia are still poorly understood. We aimed to work over metabolite biomarkers to improve mechanistic understanding of phenotypic heterogeneity and hence better management of disorder at different levels. Untargeted serum metabolites were analyzed after protein precipitation and SPE (solid phase extraction) from 100 β-thalassemia patients and 61 healthy controls using GC-MS. 40 metabolites were identified having a significance difference between these two groups at probability of 0.05 and fold change >1.5. Out of these 40 metabolites, 17 were up-regulated while 23 were down-regulated. PCA and PLS-DA model was also created that revealed a fine separation with a sensitivity of 70% and specificity of 100% on external validation of samples. Metabolic pathway analysis revealed alteration in multiple pathways including glycolysis, pyruvate, propanoate, glycerophospholipid, galactose, fatty acid, starch and sucrose metabolism along with fatty acid elongation in mitochondria, glycerolipid, glyoxylate and dicarboxylate metabolism pointing towards the shift of metabolism in β-thalassemia patients in comparison to healthy individuals.
authors.affiliation: H.E.J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi-75270, Pakistan.|Dr. Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical and Biological Sciences, University of Karachi, Karachi-75270, Pakistan.
authors.forename: Syed Ghulam
authors.initials: SG
authors.lastname: Musharraf
authors.affiliation: Dr. Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical and Biological Sciences, University of Karachi, Karachi-75270, Pakistan.
authors.forename: Ayesha
authors.initials: A
authors.lastname: Iqbal
authors.affiliation: Department of Pediatric Hematology &Molecular Medicine, National Institute of Blood Diseases and Bone Marrow Transplantation, Karachi-75300, Pakistan.
authors.forename: Saqib Hussain
authors.initials: SH
authors.lastname: Ansari
authors.affiliation: Department of Pediatric Hematology &Molecular Medicine, National Institute of Blood Diseases and Bone Marrow Transplantation, Karachi-75300, Pakistan.
authors.forename: Sadia
authors.initials: S
authors.lastname: Parveen
authors.affiliation: Dr. Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical and Biological Sciences, University of Karachi, Karachi-75270, Pakistan.
authors.forename: Ishtiaq Ahmad
authors.initials: IA
authors.lastname: Khan
authors.affiliation: H.E.J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi-75270, Pakistan.
authors.forename: Amna Jabbar
authors.initials: AJ
authors.lastname: Siddiqui
mesh_terms: D016022:Case-Control Studies; D016002:Discriminant Analysis; D015536:Down-Regulation / Q000235:genetics; D006801:Humans; D016018:Least-Squares Analysis; D055442:Metabolome; D055432:Metabolomics; D025341:Principal Component Analysis; D015854:Up-Regulation / Q000235:genetics; D017086:beta-Thalassemia / Q000378:metabolism*