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Comparative Study
. 2017 Feb 13:7:42249.
doi: 10.1038/srep42249.

β-Thalassemia Patients Revealed a Significant Change of Untargeted Metabolites in Comparison to Healthy Individuals

Syed Ghulam Musharraf  1   2 , Ayesha Iqbal  2 , Saqib Hussain Ansari  3 , Sadia Parveen  3 , Ishtiaq Ahmad Khan  2 , Amna Jabbar Siddiqui  1
Affiliations
Comparative Study

β-Thalassemia Patients Revealed a Significant Change of Untargeted Metabolites in Comparison to Healthy Individuals

Syed Ghulam Musharraf et al. Sci Rep. .

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.

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Conflict of interest statement

The authors declare no competing financial interests.

Figures

Figure 1
Figure 1. Eight metabolites at FC >2, out of which 4 are down-regulated (bar below the baseline of 0) while 4 are up-regulated (bar above the baseline of 0) in β-thalassemia patients as compared to healthy group.
Figure 2
Figure 2. PCA score plot of healthy and β-thalassemia patients based on forty (40) significantly differentiated metabolites i.e. having a fold change >1.5.
Variance on X, Y and Z axis is also shown within brackets.
Figure 3
Figure 3. PLSDA scores scatter plots discerning among healthy controls and β-thalassemia patients based on forty (40) significantly differentiated metabolites i.e. having a fold change >1.5.
Figure 4
Figure 4. Image of heatmap using non-average samples with normalized intensities of 40 significant metabolites that showed significant difference among healthy & disease group.
The arrows indicate the up-regulation and down-regulation of metabolites.
See this image and copyright information in PMC

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