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Impact of hydroxyurea therapy on serum fatty acids of β-thalassemia patients


Introduction and objective

Fatty acids (FAs) influence cell and tissue metabolism, function, responsiveness to hormonal and other signals in addition to maintenance of membrane integrity of cells. β-Thalassemia is a prevalent inherited blood disorder characterized by abnormal red cell membrane structure and function. Induction of HbF by hydroxyurea (HU) is an enduring therapeutic intervention to manage this. Therefore, in the present study we have carried out the quantification of thirteen free fatty acids to disclose the prognosis of HU in β-thalassemia.


FAs quantification was carried out using GC–MRM–MS method in the serum of 98 cases of β-thalassemia patients and out of which samples from 34 patients were collected before and after treatment with HU in addition to healthy controls (n = 31).


Using the combination of random forest (RF) with GC–MRM–MS we were able to establish a classification and prediction model that can discriminate the β-thalassemia from healthy as well as from HU treated group. Docosanoic acid (C-22:0) was most significantly altered in β-thalassemia as compared to healthy at p-value of 8.3 × 10−09 while erucic acid (C-22:1 Δcis-13) can be used as potential marker of HU prognosis because its level became significantly dissimilar at p-value of 3.7 × 10−04 in same patients in response to HU. However, nervonic acid (C-24:1 Δcis-15) was found to be the key player in effectively separating three groups.


In inference, we have noticed that HU therapy also rectifies the serum fatty acid profile in addition to its reported affect i.e. HbF induction in β-thalassemia patients.

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Fig. 1
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Fig. 5



Fetal hemoglobin




Good responders to HU therapy


Partial responders to HU therapy


Non-responders to HU therapy


The International council for harmonization of technical requirements for pharmaceuticals for human use


Good clinical practice


Random forests


Gas chromatography–multiple reaction monitoring–mass spectrometry


Fatty acids


Free fatty acids


Fatty acids methyl esters

MDS plot:

Multidimensional scaling


Principal component analysis


Variable importance plot


Total ion chromatograms


Mono unsaturated fatty acid




Central nervous system


Peripheral nervous system


Iron deficiency anemia


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The authors are thankful to all individuals who provide us their samples (blood) on voluntarily basis. This work was supported by HEJRIC (Hussain Ebraheem Jamal Research Institute of Chemistry), ICCBS University of Karachi.


No Funding was received for this research work and was only supported by the principal investigating institute i.e. HEJRIC, ICCBS, University of Karachi.

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Authors and Affiliations



SGM proposed the subject, designed the study, provided conceptual and technical guidance, along with the laboratory equipment and expertise to conduct analysis, and actively participated in manuscript writing. AI managed the procurement of healthy blood samples, actively performed experiments, interpreted data and wrote the manuscript. AJS actively participated in method optimization and data interpretation. J-HH carried out the statistical analysis of data. SHA was involved in the sample collection from β-thalassemia patients and their pathological characterization. All authors have read and approved the final manuscript.

Corresponding author

Correspondence to Syed Ghulam Musharraf.

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Conflict of interest

All the authors declare that they have no conflict of interests relevant to this study.

Ethical approval

The present study was approved by the Institutional Review Board/Ethic Committee of the hospital [National Institute of Blood Disease and Bone Marrow Transplantation (NIBD), Karachi, Pakistan] (BTIHS-KHUT-001) as per ICH GCP guidelines and from the principal investigating institute (ICCBS) (-023-HB-2017). All procedures performed in this study involving human participants were in accordance with the 1964 Helsinki declaration and its later amendments.

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Informed consent was obtained from all individual participants of this study or from their guardians.

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Iqbal, A., Siddiqui, A.J., Huang, JH. et al. Impact of hydroxyurea therapy on serum fatty acids of β-thalassemia patients. Metabolomics 14, 27 (2018).

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  • β-Thalassemia
  • Fatty acids
  • Hydroxyurea